COVID-19 Endocrinopathy with Hindsight from SARS.
This article summarizes the impact of SARS-CoV and SARS-CoV-2 on the endocrine system to facilitate our understanding of the nature of coronavirus-associated endocrinopathy. Although new data are rapidly accumulating on this novel infection, many of the endocrine manifestations of COVID-19 remain incompletely elucidated. We hereby summarize various endocrine dysfunctions including coronavirus-induced new onset diabetes mellitus, hypocortisolism, thyroid hormone and reproductive system aberrations so that clinicians armed with such insights can potentially benefit COVID-19 patients at the bedside. PMID: 33236920 [PubMe...
Source: American Journal of Physiology. Endocrinology and Metabolism - November 25, 2020 Category: Physiology Authors: Kothandaraman N, Anantharaj R, Xue B, Yew WS, Velan SS, Karnani N, Leow MK Tags: Am J Physiol Endocrinol Metab Source Type: research

Control of adipogenic commitment by a stat3-vstm2a axis.
CONTROL OF ADIPOGENIC COMMITMENT BY A STAT3-VSTM2A AXIS. Am J Physiol Endocrinol Metab. 2020 Nov 16;: Authors: Al Dow M, Silveira MAD, Poliquin A, Tribouillard L, Fournier É, Trébaol E, Secco B, Villot R, Tremblay F, Bilodeau S, Laplante M Abstract White adipose tissue (WAT) is a dynamic organ that plays crucial roles in controlling metabolic homeostasis. During development and periods of energy excess, adipose progenitors are recruited and differentiate into adipocytes to promote lipid storage capability. The identity of adipose progenitors and the signals that promote their recruitment...
Source: American Journal of Physiology. Endocrinology and Metabolism - November 16, 2020 Category: Physiology Authors: Al Dow M, Silveira MAD, Poliquin A, Tribouillard L, Fournier É, Trébaol E, Secco B, Villot R, Tremblay F, Bilodeau S, Laplante M Tags: Am J Physiol Endocrinol Metab Source Type: research

Regulation of direct adipose tissue free fatty acid storage during mixed meal ingestion and high free fatty acid concentration conditions.
Abstract Direct free fatty acid (FFA) storage into adipocytes relates to body fat distribution. Adipose tissue CD36, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) may account for some of the between-depot and inter-individual variability in FFA storage. These studies were to test whether CD36, ACS or DGAT might be important for direct palmitate storage under meal-ingestion or high FFA conditions. We measured upper (UBSQ) and lower body subcutaneous (LBSQ) adipose tissue FFA storage rates by infusing palmitate tracers intravenously and performing adipose biopsies under hypoinsulinemic (hig...
Source: American Journal of Physiology. Endocrinology and Metabolism - November 16, 2020 Category: Physiology Authors: Zhang L, Hames KC, Jensen MD Tags: Am J Physiol Endocrinol Metab Source Type: research

SARS-CoV-2: Influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP)-metabolism and on severity of COVID-19.
Abstract The use of vitamin D to reduce the severity of COVID-19 complications is receiving considerable attention, backed by encouraging data. Its purported mode of action is as an immune modulator. Vitamin D, however, also affects metabolism of phosphate and Mg, which may well play a critical role in SARS-CoV-2 pathogenesis. SARS-CoV-2 may induce a cytokine storm that drains ATP whose regeneration requires phosphate and Mg. These minerals, however, are often deficient in conditions that predispose people to severe COVID-19, including older age (especially males), diabetes, obesity, and usage of diuretics. Sympto...
Source: American Journal of Physiology. Endocrinology and Metabolism - November 11, 2020 Category: Physiology Authors: van Kempen TA, Deixler E Tags: Am J Physiol Endocrinol Metab Source Type: research

Adipsin deficiency does not impact atherosclerosis development in Ldlr-/- mice.
CONCLUSIONS: Adipsin deficiency does not impact the development of atherosclerosis in Ldlr-/-mice despite its crucial function in alternative complement activation. Therefore, it is unlikely to play an important role in mediating the risk of atherosclerotic complications in obesity. PMID: 33135458 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - November 2, 2020 Category: Physiology Authors: Liu L, Chan M, Yu L, Wang W, Qiang L Tags: Am J Physiol Endocrinol Metab Source Type: research

Dihydroceramides: Their emerging physiological roles and functions in cancer and metabolic diseases.
Abstract Dihydroceramides are a type of sphingolipids that for a long time were regarded as biologically inactive. They are metabolic intermediates of the de novo sphingolipid synthesis pathway, and are converted into ceramides with the addition of a double bond. Ceramides are abundant in tissues and have well-established biological functions. On the contrary, dihydroceramides are less prevalent and despite their hitherto characterization as inert lipids, studies of the last decade begun to unravel their implication in various biological processes distinct from those involving ceramides. These processes include ce...
Source: American Journal of Physiology. Endocrinology and Metabolism - November 2, 2020 Category: Physiology Authors: Lachkar F, Ferre P, Foufelle F, Papaioannou A Tags: Am J Physiol Endocrinol Metab Source Type: research

Assessment of individual and standardized Glucagon kinetics for the estimation of Glucagon secretion in healthy humans.
Abstract Impaired glucose tolerance arises out of impaired postprandial insulin secretion and delayed suppression of glucagon. These defects occur early and independently in the pathogenesis of prediabetes. Quantification of the contribution of α-cell dysfunction to glucose tolerance has been lacking because knowledge of glucagon kinetics in humans is limited. Therefore, in a series of experiments examining the interaction of glucagon suppression with insulin secretion we studied 51 non-diabetic subjects (age = 54 ± 13 years, BMI = 28 ± 4 Kg/m2). Glucose was infused to mimic the systemic appear...
Source: American Journal of Physiology. Endocrinology and Metabolism - November 2, 2020 Category: Physiology Authors: Laurenti MC, Vella A, Adams JD, Schembri Wismayer DJ, Egan AM, Dalla Man C Tags: Am J Physiol Endocrinol Metab Source Type: research

Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER) α.
Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER)α. Am J Physiol Endocrinol Metab. 2020 Nov 02;: Authors: Buscato M, Davezac M, Zahreddine R, Adlanmerini M, Metivier R, Fillet M, Cobraiville G, Moro C, Foidart JM, Lenfant F, Gourdy P, Arnal JF, Fontaine C Abstract Estetrol (E4), a natural estrogen synthesized by the human fetal liver, is currently evaluated in phase III clinical studies as a new menopause hormone therapy. Indeed, E4 significantly improves vasomotor and genito-urinary menopausal symptoms and prevents bone demineralization....
Source: American Journal of Physiology. Endocrinology and Metabolism - November 2, 2020 Category: Physiology Authors: Buscato M, Davezac M, Zahreddine R, Adlanmerini M, Metivier R, Fillet M, Cobraiville G, Moro C, Foidart JM, Lenfant F, Gourdy P, Arnal JF, Fontaine C Tags: Am J Physiol Endocrinol Metab Source Type: research

Effects of carbohydrate restriction on postprandial glucose metabolism, beta-cell function, gut hormone secretion, and satiety in patients with type 2 diabetes.
Abstract Background & Aims Dietary carbohydrate-restriction may improve the phenotype of type 2 diabetes (T2D) patients. We aimed to investigate 6 weeks of carbohydrate-restriction on postprandial glucose metabolism, pancreatic alpha- and beta-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a cross-over design, 28 T2D patients (mean: HbA1c 60 mmol/mol) were randomized to 6 weeks of carbohydrate-reduced high-protein (CRHP) diet and 6 weeks of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 versus 50/17/33). Twenty-four-hour continuous glucose m...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Skytte MJ, Samkani A, Astrup A, Frystyk J, Rehfeld JF, Holst JJ, Madsbad S, Burling K, Fenger M, Thomsen MN, Larsen TM, Krarup T, Haugaard SB Tags: Am J Physiol Endocrinol Metab Source Type: research

The Fascinating Physiology of Insulin: Celebrating a Centennial Hormone.
PMID: 33103449 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Marette A Tags: Am J Physiol Endocrinol Metab Source Type: research

Holistic Characterization of Single Hepatocyte Transcriptome Responses to High Fat Diet.
In conclusion, our dataset provides a useful resource for understanding hepatocellular alteration during NAFLD at single cell level. PMID: 33103450 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Park SR, Cho CS, Xi J, Kang HM, Lee JH Tags: Am J Physiol Endocrinol Metab Source Type: research

Differential responses of bone to angiotensin II and angiotensin(1-7): beneficial effects of Ang(1-7) on bone with exposure to high glucose.
This study aimed to explore the respective effect of angiotensin II (Ang II) and angiotensin(1-7) [Ang(1-7)], active peptides in the renin-angiotensin system, on osteoblasts and osteoclasts under high glucose, as well as to investigate the osteo-preservative effects of Ang II type 1 receptor (AT1R) blocker and Ang(1-7) in diabetic spontaneously hypertensive rats (SHR). Ang II and Ang(1-7) respectively decreased and increased the formation of calcified nodules and ALP activity in MC3T3-E1 cells under high glucose, and respectively stimulated and inhibited the number of matured osteoclasts and pit resorptive area in RANKL-in...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Sha NN, Zhang JL, Poon CC, Li WX, Li Y, Wang YF, Shi W, Lin FH, Lin WP, Wang YJ, Zhang Y Tags: Am J Physiol Endocrinol Metab Source Type: research

AMPK mediates regulation of voltage-gated calcium channels by leptin in orexigenic neurons from arcuate nucleus.
Abstract Neuronal control of the energy homeostasis requires the arcuate nucleus of hypothalamus. This structure integrates peripheral and central signals concerning the energy state of the body. It is comprised of two populations of neurons releasing anorexigenic and orexigenic peptides amongst others. Both populations are regulated by leptin, an anorexigenic hormone released by white adipose tissue. Voltage-gated calcium entry is critical to promote neurotransmitter and hormone release. It is already known that calcium channel current is inhibited by leptin in orexigenic neurons. However, fine-tuning details of ...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Bermeo K, Castro H, Arenas I, Garcia DE Tags: Am J Physiol Endocrinol Metab Source Type: research

Effect of Hypoxic Exercise on Glucose Tolerance in Healthy and Pre-diabetic Adults.
CONCLUSIONS: Our results show that an acute bout of exercise in hypoxia reduces glucose tolerance in healthy and pre-diabetic subjects. At a molecular level, some adaptations regulating glucose transport in muscle were found in all groups without associations with glucose tolerance after exercise. The results suggest that hypoxia negatively affects glucose tolerance post-exercise through unidentified mechanisms. PMID: 33103453 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: De Groote E, Britto FA, Balan E, Warnier G, Thissen JP, Nielens H, Sylow L, Deldicque L Tags: Am J Physiol Endocrinol Metab Source Type: research

GPR40-Deficiency Is Associated with Hepatic FAT/CD36 Upregulation, Steatosis, Inflammation and Cell Injury in C57BL/6 Mice.
In this study, we fed wild-type or GPR40 knockout C57BL/6 mice high-fat diet (HFD) for 20 weeks and then assessed the effect of GPR40-deficiency on HFD-induced NAFLD. Assays on metabolic parameters showed that HFD increased bodyweight, glucose, insulin, insulin resistance, cholesterol and alanine aminotransferase (ALT), and GPR40-deficiency did not mitigate the HFD-induced metabolic abnormalities. In contrast, we found that GPR40-deficiency was associated with increased bodyweight, insulin, insulin resistance, cholesterol and ALT in control mice fed low fat diet (LFD). Surprisingly, histology and Oil Red O staining showed ...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Lu Z, Li Y, Syn WK, Li AJ, Ritter S, Wank SA, Lopes-Virella MF, Huang Y Tags: Am J Physiol Endocrinol Metab Source Type: research

Paracrine and autocrine control of insulin secretion in human islets: evidence and pending questions.
Abstract Insulin secretion by β-cells is largely controlled by circulating nutrients, hormones and neurotransmitters. However, recent years have witnessed the multiplication of studies investigating whether local regulation also takes place within pancreatic islets, in which β-cells cohabit with several other cell types. The cell composition and architectural organization of human islets differ from those of rodent islets and are particularly favorable to cellular interactions. An impressive number of hormonal (glucagon, glucagon-like peptide1, somatostatin...) and non-hormonal products (ATP, acetylcholi...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Henquin JC Tags: Am J Physiol Endocrinol Metab Source Type: research

Mesenchymal stem cells alleviate palmitic acid induced endothelial to mesenchymal transition by suppressing endoplasmic reticulum stress.
Abstract High levels of plasma free fatty acids (FFAs) lead to endothelial dysfunction (ED), which is involved in the pathogenesis of Metabolic Syndrome, diabetes as well as atherosclerosis. ER stress and Endothelial-to-mesenchymal transition (EndMT) are demonstrated mechanistically related to endothelial dysfunction. Mesenchymal stem cells (MSCs) have exhibited an extraordinary cytoprotective effect on cellular lipotoxicity and vasculopathy. However, the underlying mechanisms have not been clearly defined. In the present study, we investigated whether MSCs could ameliorate palmitic acid (PA) - induced endothelial...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 12, 2020 Category: Physiology Authors: Luo R, Li L, Liu X, Yuan Y, Zhu W, Li L, Liu J, Lu Y, Cheng J, Chen Y Tags: Am J Physiol Endocrinol Metab Source Type: research

Co-impairment of autonomic and glucagon responses to insulin-induced hypoglycemia in dogs with naturally-occurring insulin-dependent diabetes mellitus.
CONCLUSIONS: 1) Impairment of glucagon responses in DMN dogs is not due to generalized impairment of alpha-cell function. 2) Loss of tonic inhibition of glucagon secretion by insulin is not sufficient to produce loss of the glucagon response; impairment of autonomic activation is also required. 3) In dogs with major beta-cell function loss, activation of the autonomic inputs is sufficient to mediate an intact glucagon response to IIH. PMID: 33044845 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - October 12, 2020 Category: Physiology Authors: Gilor C, Duesberg C, Elliott DA, Feldman EC, Mundinger TO, Taborsky GJ, Nelson RW, Havel PJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Diet during early life defines testicular lipid content and sperm quality in adulthood.
F, Alves MG Abstract Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health but few studies addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism leading to permanent damage to sperm parameters. After weaning (day 21 after birth), 36 male mice were randomly divided into 3 groups and fed with different diet regimen for 200 days: CTRL-standard chow; HFD-high-fat diet (Carbohydrate: 35.7%, Protein: 20.5%, Fat...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 12, 2020 Category: Physiology Authors: Crisóstomo L, Videira RA, Jarak I, Starčević K, Mašek T, Rato LP, Raposo JF, Batterham RL, Oliveira PF, Alves MG Tags: Am J Physiol Endocrinol Metab Source Type: research

Oral and Intestinal Microbial Features in Pregnant Women with Hypothyroidism and Their Correlations with Pregnancy Outcomes.
CONCLUSION: There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy. PMID: 33017219 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - October 4, 2020 Category: Physiology Authors: Wang B, Xu Y, Zhang M, Zhang J, Hou X, Li J, Cai Y, Sun Z, Ban Y, Wang W Tags: Am J Physiol Endocrinol Metab Source Type: research

GLP1 Receptor Agonism Protects Against Acute Olanzapine Induced Hyperglycemia.
Abstract Olanzapine is a second-generation antipsychotic (SGA) used in the treatment of schizophrenia and a number of off-label conditions. While effective in reducing psychoses, acute olanzapine treatment causes hyperglycemia. Pharmacological agonists of the glucagon-like peptide-1 (GLP1) receptor have been shown to offset weight-gain associated with chronic SGA administration. It is not known if GLP-1 receptor agonism would mitigate the acute metabolic side effects of SGAs. Within this context, we sought to determine if pharmacological targeting of the GLP1 receptor would be sufficient to protect against acute o...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 4, 2020 Category: Physiology Authors: Medak KD, Shamshoum H, Peppler WT, Wright DC Tags: Am J Physiol Endocrinol Metab Source Type: research

Loss of CTRP4 alters adiposity and food intake behaviors in obese mice.
Abstract Central and peripheral mechanisms are both required for proper control of energy homeostasis. Among circulating plasma proteins, C1q/TNF-related proteins (CTRPs) recently emerged as important regulators of sugar and fat metabolism. CTRP4, expressed in brain and adipose tissue, is unique among the family members in having two tandem globular C1q domains. We previously showed that central administration of recombinant CTRP4 suppresses food intake, suggesting a central nervous system role in regulating ingestive physiology. Whether this effect is pharmacologic or physiologic remains unclear. We used a loss-o...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 4, 2020 Category: Physiology Authors: Sarver DC, Stewart AN, Rodriguez S, Little HC, Aja S, Wong GW Tags: Am J Physiol Endocrinol Metab Source Type: research

New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity.
Abstract Xanthine oxidoreductase (XOR) consists of two different forms, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), and is a rate-limiting enzyme of uric acid production from hypoxanthine and xanthine. Uric acid is the end-product of purine metabolism in humans and has a powerful antioxidant effect. The lack of ascorbic acid, known as vitamin C, in hominoids has been thought to cause a compensatory increase in uric acid as an antioxidant by unfunctional gene mutation of uricase to a pseudogene. Since XO is involved in an increase in reactive oxygen species (ROS) by generating superoxide and hydrogen pe...
Source: American Journal of Physiology. Endocrinology and Metabolism - September 6, 2020 Category: Physiology Authors: Furuhashi M Tags: Am J Physiol Endocrinol Metab Source Type: research

Targeting FFA1 and FFA4 receptors in cancer-induced cachexia.
os MM Abstract Free fatty acid (FFA) receptors FFA1 and FFA4 are omega-3 molecular targets in metabolic diseases; however, their function in cancer cachexia remains unraveled. We assessed the role of FFA1 and FFA4 receptors in the mouse model of cachexia induced by Lewis lung carcinoma (LLC) cell implantation. Naturally-occurring ligands α-linolenic acid (ALA) and docosahexaenoic acid (DHA), the synthetic FFA1/FFA4 agonists GW9508 and TUG891, or the selective FFA1 GW1100 or FFA4 AH7614 antagonists were tested. FFA1 and FFA4 expression and other cachexia-related parameters were evaluated. GW9508 and TUG891 de...
Source: American Journal of Physiology. Endocrinology and Metabolism - September 6, 2020 Category: Physiology Authors: Freitas RDS, Muradás TC, Dagnino APA, Rost FL, Costa KM, Venturin GT, Greggio S, da Costa JC, Campos MM Tags: Am J Physiol Endocrinol Metab Source Type: research

The emerging role of lactate as a mediator of exercise-induced appetite suppression.
Abstract Lactate, a molecule originally considered metabolic waste, is now associated with a number of important physiological functions. Although the roles of lactate as a signaling molecule, fuel source, and gluconeogenic substrate have garnered significantly attention in recent reviews, a relatively underexplored and emerging role of lactate is its control of energy intake (EI). To expand our understanding of the physiological roles of lactate, we present evidence from early infusion studies demonstrating the ability of lactate to suppress EI in both rodents and humans. We then discuss findings from recent huma...
Source: American Journal of Physiology. Endocrinology and Metabolism - September 6, 2020 Category: Physiology Authors: McCarthy SF, Islam H, Hazell TJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Physiological profile regulation during weight gain and loss by ovariectomized females: importance of SIRT1 and SIRT4.
CONCLUSION: Weight cycle suggested that mitochondrial and nuclear sirtuins were active in cellular signaling for the control lipids metabolism, oxidative phosphorylation and redox status. Weight cycling was able to restore the characteristics of the health of lean animals. PMID: 32865007 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - August 30, 2020 Category: Physiology Authors: Camargo TF, Zanesco AM, Pacher KAS, Andrade TAM, Alves AA, do Amaral MEC Tags: Am J Physiol Endocrinol Metab Source Type: research

IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3k-Akt-mTOR pathway and GPER.
Abstract Autophagy dysfunctions are involved in the pathogenesis of Parkinson disease (PD). In the present study, we aimed to evaluate the involvement of G-protein coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treatment significantly induced mice movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed signifi...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 30, 2020 Category: Physiology Authors: Wang XW, Yuan LJ, Yang Y, Zhang M, Chen WF Tags: Am J Physiol Endocrinol Metab Source Type: research

Beta-cell specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.
Abstract Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing post-translational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in mitochondria. We showed that mice with a global loss of SIRT4 (SIRT4KO mice) developed an increase in glucose- and leucine-stimulated insulin secretion, and this was followed by accelerated age-induced glucose intolerance and insulin resistance. Since whole body SIRT4KO mice had alterations to nutrient-stimulated insulin secretion, we hypothesized that...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 30, 2020 Category: Physiology Authors: Huynh FK, Peterson BS, Anderson KA, Lin Z, Coakley AJ, Llaguno FMS, Nguyen TN, Campbell JE, Stephens SB, Newgard CB, Hirschey MD Tags: Am J Physiol Endocrinol Metab Source Type: research

Ischemic preconditioning prevents impact of prolonged sitting on glucose tolerance and markers of cardiovascular health, but not cerebrovascular responses.
We examined whether ischemic preconditioning (IPC) prevents the impact of prolonged sitting-induced glucose intolerance, and measured related influencing factors such as (para)sympathetic nerve activity (assessed by heart rate variability (HRV)) and blood pressure during 2h prolonged sitting. In this randomized, controlled cross-over study, 15 healthy participants (80% men) with a mean age of 21±1 years (means±SD) and body mass index of 25.0±2.4 kg m2 performed IPC (IPC; 4×5-min 220-mmHg unilateral occlusion at the thigh muscle) or a sham intervention (Sham; 4×5-min 20-mmHg), followed by 2h...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 30, 2020 Category: Physiology Authors: Horiuchi M, Thijssen DHJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Worsening Baroreflex Sensitivity on Progression to Type II Diabetes: Localized vs. Systemic Inflammation and Role of Antidiabetic Therapy.
Abstract Cardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hyp...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 30, 2020 Category: Physiology Authors: Bakkar NMZ, Mougharbil N, Mroueh A, Kaplan A, Eid AH, Fares SA, Zouein F, El-Yazbi A Tags: Am J Physiol Endocrinol Metab Source Type: research

Salicylate administration suppresses the inflammatory response to nutrients and improves ovarian function in polycystic ovary syndrome.
We examined the effects of salsalate treatment on nutrient-induced OS and inflammation, ovarian androgen secretion, ovulation and insulin sensitivity. Eight lean insulin-sensitive women with PCOS and 8 age- and body composition-matched ovulatory controls for baseline comparison participated in the study. The women with PCOS underwent a 12-week treatment of salsalate, a non-steroidal anti-inflammatory drug, at a dose of 3 gm daily. Markers of OS and inflammation were quantified in mononuclear cells (MNC) and plasma from blood drawn fasting and 2 hours after saturated fat ingestion, before and after treatment. Ovarian androg...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Gonzalez F, Mather KJ, Considine RV, Abdelhadi OA, Acton AJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Caloric Restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination and insulin secretion in prediabetic mice.
Caloric Restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination and insulin secretion in prediabetic mice. Am J Physiol Endocrinol Metab. 2020 Aug 24;: Authors: do Amaral MEC, Kravets V, Dwulet JM, Farnsworth NL, Piscopio R, Schleicher WE, Miranda JG, Benninger RKP Abstract Caloric restriction can decrease the incidence of metabolic diseases such as obesity and type 2 diabetes mellitus (T2DM). The mechanisms underlying the benefits of caloric restriction involved in insulin secretion and glucose homeostasis are not fully understood. Intercellular c...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: do Amaral MEC, Kravets V, Dwulet JM, Farnsworth NL, Piscopio R, Schleicher WE, Miranda JG, Benninger RKP Tags: Am J Physiol Endocrinol Metab Source Type: research

Transcription Factor EB (TFEB): new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?
Abstract In response to the increased energy demands of contractions, skeletal muscle adapts remarkably well through acutely regulating metabolic pathways to maintain energy balance and in the longer term by regulating metabolic reprogramming such as remodeling and expanding the mitochondrial network. This long-term adaptive response involves modulation of gene expression at least partly through the regulation of specific transcription factors and transcriptional coactivators. The AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor-γ co-activator 1a (PGC1a) pathway has long been kn...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Markby GR, Sakamoto K Tags: Am J Physiol Endocrinol Metab Source Type: research

Exacerbated obesogenic response in female mice exposed to early life stress is linked to fat depot-specific upregulation of leptin protein expression.
Abstract Early life stress (ELS) is an independent risk factor for increased BMI and cardiometabolic disease risk later in life. We have previously shown that a mouse model of ELS, Maternal Separation and Early Weaning (MSEW), exacerbates high fat diet (HF)-induced obesity only in adult female mice. The aim of this study was to investigate: 1) whether the short- and long-term effects of HF on leptin expression are influenced by MSEW in a sex-specific manner, and 2) the potential epigenetic mechanisms underlying the MSEW-induced changes in leptin expression. After 1-week of HF, both MSEW male and female mice displa...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Leachman JR, Rea M, Cohn DM, Xu X, Fondufe-Mittendorf Y, Loria AS Tags: Am J Physiol Endocrinol Metab Source Type: research

Elevated plasma lactate levels via exogenous lactate infusion do not alter resistance exercise-induced signaling or protein synthesis in human skeletal muscle.
erg M Abstract Lactate has been implicated as a potential signaling molecule. In myotubes, lactate incubation increases mTORC1- and ERK-signaling and induces hypertrophy, indicating that lactate could be a mediator of muscle adaptations to resistance exercise. However, the potential signaling properties of lactate, at rest or with exercise, have not been explored in human tissue. In a cross-over design study, 8 men and 8 women performed one-legged resistance exercise while receiving venous infusion of saline or sodium lactate. Blood was sampled repeatedly, and muscle biopsies were collected at rest and at 0, 90,18...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Liegnell R, Apró W, Danielsson S, Ekblom B, van Hall G, Holmberg HC, Moberg M Tags: Am J Physiol Endocrinol Metab Source Type: research

Hyperglycemia does not Inhibit Insulin's Effects on Microvascular Perfusion in Healthy Humans: A Randomized Crossover Study.
Abstract Diabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared to normoglycemic controls. Currently there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiologic factors (e.g., vasoactive hormones) contribute. To our knowledge, no prior studies have examined the dynamic effects of acute hyperglycemia on insulin-mediated a...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Horton WB, Jahn LA, Hartline LM, Aylor KW, Patrie JT, Barrett EJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Comparison of the effects of soluble corn fiber and fructooligosaccharides on metabolism, inflammation and gut microbiome of high-fat diet fed mice.
Abstract Dietary fibers are essential components of a balanced diet and have beneficial effects on metabolic functions. To gain insight into their impact on host physiology and gut microbiota, we performed a direct comparison of two specific prebiotics fibers in mice. During an 8-week follow up, mice fed a high-fat diet (HFD) were compared to mice on a normal diet (basal condition, controls) and to mice fed the HFD but treated with one of the following prebiotics: Fructooligosaccharides (FOS) or soluble corn fiber (SCF). Both prebiotic fibers led to a similar reduction of body weight and fat mass, lower inflammati...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Van Hul M, Karnik K, Canene-Adams K, De Souza M, Van den Abbeele P, Marzorati M, Delzenne NM, Everard A, Cani PD Tags: Am J Physiol Endocrinol Metab Source Type: research

Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver.
Abstract The effect of chronic of hyperinsulinemia in the fetal liver is poorly understood. Here, we produced hyperinsulinemia with euglycemia for ~8 days in fetal sheep (INS) at 0.9 gestation. INS fetuses had increased insulin and decreased oxygen and amino acid (AA) concentrations compared to saline infused fetuses (CON). Glucose (whole-body) utilization rates were increased, as expected, in INS fetuses. In the liver, however, there were few differences in genes and metabolites related to glucose and lipid metabolism and no activation of insulin signaling proteins (AKT and mTOR). There was increased P-AMPK activ...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 23, 2020 Category: Physiology Authors: Rozance PJ, Jones AK, Bourque SL, D'Alessandro A, Hay WW, Brown LD, Wesolowski SR Tags: Am J Physiol Endocrinol Metab Source Type: research

miR-30a targets gene networks that promote browning of human and mouse adipocytes.
Abstract MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to anti-diabetic peroxisome proliferator-activated receptor gamma (PPARγ) agonist activity and metabolic functions in adipocytes. We found WAT isolated from diabetic patients show reduced mi...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 16, 2020 Category: Physiology Authors: Saha PK, Hamilton MP, Rajapakshe K, Putluri V, Felix JB, Masschelin P, Cox AR, Bajaj M, Putluri N, Coarfa C, Hartig SM Tags: Am J Physiol Endocrinol Metab Source Type: research

Mitochondrial-derived peptides in energy metabolism.
Abstract Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open reading frames (sORF) in mitochondrial DNA that do not necessarily have traditional hallmarks of protein-coding genes. To date, eight MDPs have been identified, all of which have been shown to have various cyto- or metabolo-protective properties. The 12S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, while the other seven MDPs, [humanin and small humanin-like peptides (SHLP) 1-6] are encoded by the 16S ribosomal RNA gene. Here we review the evidence that endogenous MDPs are sensitive to changes in metab...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 9, 2020 Category: Physiology Authors: Merry TL, Chan A, Woodhead JST, Reynolds JC, Kumaga H, Kim SJ, Lee C Tags: Am J Physiol Endocrinol Metab Source Type: research

Overexpression of histone deacetylase SIRT1 exerts an anti-angiogenic role in diabetic retinopathy via miR-20a elevation and YAP/HIF1 α/VEGFA depletion.
Overexpression of histone deacetylase SIRT1 exerts an anti-angiogenic role in diabetic retinopathy via miR-20a elevation and YAP/HIF1α/VEGFA depletion. Am J Physiol Endocrinol Metab. 2020 Aug 10;: Authors: Pan Q, Gao Z, Zhu C, Peng Z, Song M, Li L Abstract As a basic member of the Class III histone deacetylases, SIRT1 has been implicated in the occurrence and progression of diabetic retinopathy (DR). The current study aimed to investigate the roles of SIRT1/miR-20a/YAP/HIF1α/VEGFA in DR. The expression of SIRT1 was initially determined through RT-qPCR and western blot analysis following th...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 9, 2020 Category: Physiology Authors: Pan Q, Gao Z, Zhu C, Peng Z, Song M, Li L Tags: Am J Physiol Endocrinol Metab Source Type: research

Intestinal NAPE-PLD contributes to short-term regulation of food intake via gut to brain axis.
CONCLUSIONS: In response to lipid, NapepldΔIEC mice displayed reduced OEA in brain and intestine, suggesting an impairment of the gut-brain axis in this model. We speculated that decreased level of OEA likely contributes to reduce GLP-1R activation, explaining the observed hyperphagia in this model. Altogether, weelucidated novel physiological mechanism regarding the gut-brain axis by which intestinal NAPE-PLD regulates appetite rapidly after lipid exposure. PMID: 32776827 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - August 9, 2020 Category: Physiology Authors: Rastelli M, Van Hul M, Terrasi R, Lefort C, Régnier M, Beiroa D, Delzenne NM, Everard A, Nogueiras R, Luquet S, Muccioli GG, Cani PD Tags: Am J Physiol Endocrinol Metab Source Type: research

Testosterone supplementation up-regulates androgen receptor expression and translational capacity during severe energy deficit.
Abstract Testosterone supplementation during energy deficit promotes whole-body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before (Resting), 1 h (Post) and 6 h (Recovery) after exercise and a mixed meal (40 g protein, 1 h post-exercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active, non-obese men treated with 200 mg testosterone enanthate/week (TEST) or placebo (PLA) during th...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 9, 2020 Category: Physiology Authors: Howard EE, Margolis LM, Berryman CE, Lieberman HR, Karl JP, Young AJ, Montano MA, Evans WJ, Rodriguez NR, Johannsen NM, Gadde KM, Harris MN, Rood JC, Pasiakos SM Tags: Am J Physiol Endocrinol Metab Source Type: research

Endothelial dysfunction due to selective insulin resistance in vascular endothelium: insights from mechanistic modeling.
Abstract Previously, we have used mathematical modeling to gain mechanistic insight into insulin-stimulated glucose uptake. Phosphatidylinositol 3-kinase-dependent (PI3K) insulin signaling required for metabolic actions of insulin also regulates endothelium-dependent production of the vasodilator nitric oxide (NO). Vasodilation increases blood flow that augments direct metabolic actions of insulin in skeletal muscle. This is counterbalanced by mitogen-activated protein kinase (MAPK)-dependent insulin signaling in endothelium that promotes secretion of the vasoconstrictor endothelin-1 (ET-1). In the present study, ...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 9, 2020 Category: Physiology Authors: Muniyappa R, Chen H, Montagnani M, Sherman A, Quon MJ Tags: Am J Physiol Endocrinol Metab Source Type: research

May phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (covid-19)?
MAY PHYTOTHERAPY WITH POLYPHENOLS SERVE AS A POWERFUL APPROACH FOR THE PREVENTION AND THERAPY TOOL OF NOVEL CORONAVIRUS DISEASE 2019 (COVID-19)? Am J Physiol Endocrinol Metab. 2020 Aug 05;: Authors: Levy E, Delvin E, Marcil V, Spahis S Abstract Much more serious than the previous severe acute respiratory syndrome (SARS) coronavirus (CoV) outbreaks, the novel SARS-CoV-2 infection has spread speedily, affecting 213 countries and causing ~17,300,000 million cases and ~672,000 (~+1500/day) deaths globally (as of July 31th, 2020). The potentially fatal COVID-19, caused by air droplets and airborne as the m...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 4, 2020 Category: Physiology Authors: Levy E, Delvin E, Marcil V, Spahis S Tags: Am J Physiol Endocrinol Metab Source Type: research

Neurodegeneration in juvenile Iberian pigs with diet-induced non-alcoholic fatty liver disease.
In conclusion, our results show evidence of neurodegeneration in FC of juvenile Iberian pigs, and establish a novel pediatric model to investigate the role of gut-liver-brain axis in diet-induced NAFLD. PMID: 32744096 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - August 2, 2020 Category: Physiology Authors: Zeltser N, Meyer I, Hernandez GV, Trahan MJ, Fanter RK, Ismail MA, Glanz H, Strand CR, Burrin DG, La Frano MR, Manjarin R, Maj M Tags: Am J Physiol Endocrinol Metab Source Type: research

Hyperphosphorylation of fetal liver IGFBP-1 precedes slowing of fetal growth in nutrient restricted baboons and may be a mechanism underlying IUGR.
Abstract In cultured fetal liver cells, IGFBP-1 hyperphosphorylation in response to hypoxia and amino acid deprivation is mediated by inhibition of mechanistic target of rapamycin (mTOR) and activation of amino acid response (AAR) signalling and casein kinase CK2. We hypothesized that fetal liver mTOR inhibition, activation of AAR and CK2, and IGFBP-1 hyperphosphorylation occur prior to development of intrauterine growth restriction (IUGR). Pregnant baboons were fed a Control (C) or a Maternal Nutrient Restriction (MNR; 70% calories of Control) diet starting at gestational day (GD) 30 (Term GD185). Umbilical blood...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 2, 2020 Category: Physiology Authors: Kakadia JH, Jain BB, Biggar KK, Sutherland A, Nygard K, Li C, Nathanielsz PW, Jansson T, Gupta MB Tags: Am J Physiol Endocrinol Metab Source Type: research

Role for endocannabinoids in early pregnancy: Recent advances and the effects of cannabis use.
Abstract The endocannabinoid system (ECS) is associated with several physiological processes including reproduction. This system consists of the cannabinoid receptors, endocannabinoid ligands and enzymes which metabolize and degrade these fatty acids. Recent evidence shows that cannabinoid receptors are expressed in cells of the reproductive system including endometrial stromal cells, ovaries, and sperm cells. Emerging and recent research suggests that the ECS may play a significant role in reproduction. The endocannabinoid ligands anandamide and 2-arachidonoyl-glycerol are crucial for successful endometrium decid...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 2, 2020 Category: Physiology Authors: Ezechukwu HC, Diya CA, Shrestha N, Hryciw DH Tags: Am J Physiol Endocrinol Metab Source Type: research

Aerobic exercise training regulates serum extracellular vesicle miRNAs linked to obesity to promote their beneficial effects in mice.
es AC Abstract There is growing body of evidence that extracellular vesicles (EVs) and their cargo of RNA, DNA, and protein are released into the circulation with exercise and might mediate inter-organ communication. C57BL6/J male mice were diet-induced obesity and subjected to aerobic training on a treadmill for 8 weeks. The effect of aerobic training was evaluated in the liver, muscle, kidney and white/brown adipose tissue. In order to provide new mechanistic insight, we profiled miRNA from serum EVs of obese and obese trained mice. We demonstrate that aerobic training changes circulating EVs miRNA profile of ob...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 2, 2020 Category: Physiology Authors: de Mendonça M, Rocha KC, de Sousa E, Pereira BMV, Oyama LM, Rodrigues AC Tags: Am J Physiol Endocrinol Metab Source Type: research

Glucagon-like peptide-1 receptor mediates the beneficial effect of Liraglutide in an acute lung injury mouse model involving the thioredoxin interacting protein.
Abstract Repurposing clinically used drugs is among important strategies in drug discovery. Glucagon-like peptide-1 (GLP-1) and its based diabetes drugs such as Liraglutide possess a spectrum of extra-pancreatic functions, while GLP-1 receptor (GLP-1R) is most abundantly expressed in the lung. Recent studies have suggested that GLP-1-based drugs exert beneficial effects in chronic as well as acute lung injury rodent models. We show here that Liraglutide pretreatment reduced lipopolysaccharide (LPS) induced acute lung injury in mice. It significantly reduced lung injury score, wet/dry lung weight ratio, bronchoalve...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 28, 2020 Category: Physiology Authors: Zhou W, Shao W, Zhang Y, Liu D, Liu M, Jin T Tags: Am J Physiol Endocrinol Metab Source Type: research