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A gut –brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus
Conclusions We have defined a gut–brain axis that regulates glucose metabolism mediated by antagonistic fibroblast growth factors. From the intestine, bile acids stimulate FGF15 secretion, leading to activation of the FGF receptors in hypothalamic AGRP/NPY neurons. FGF receptor intracellular signaling subsequently silences AGRP/NPY neurons, leading to improvements of glucose tolerance that are likely mediated by the autonomic nervous system. Finally, short peptides that antagonize homodimeric FGF receptor signaling within the hypothalamus have beneficial effects on glucose homeostasis without inducing hypoglycemia. T...
Source: Molecular Metabolism - December 15, 2017 Category: Endocrinology Source Type: research

A gut-brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus
Conclusions We have defined a gut-brain axis that regulates glucose metabolism mediated by antagonistic fibroblast growth factors. From the intestine, bile acids stimulate FGF15 secretion, leading to activation of the FGF receptors in hypothalamic AGRP/NPY neurons. FGF receptor intracellular signaling subsequently silences AGRP/NPY neurons, leading to improvements of glucose tolerance that are likely mediated by the autonomic nervous system. Finally, short peptides that antagonize homodimeric FGF receptor signaling within the hypothalamus have beneficial effects on glucose homeostasis without inducing hypoglycemia. These p...
Source: Molecular Metabolism - December 10, 2017 Category: Endocrinology Source Type: research

The LepR-mediated leptin transport across brain barriers controls food reward
Conclusions The LepR-mediated transport of leptin across brain barriers in endothelial cells lining microvessels and in epithelial cells of the choroid plexus controls food reward but is apparently not involved in homeostatic control of feeding. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 8, 2017 Category: Endocrinology Source Type: research

Androgen receptor overexpression in prostate cancer in type 2 diabetes
Conclusions We report elevated androgen receptor signaling and activity presumably due to altered insulin/IGF-1 receptors and decreased levels of protective estrogen receptor ligands in prostate cancer in men with diabetes. Our results reveal new insights why these patients have a worse prognosis. These findings provide the basis for future clinical trials to investigate treatment response in patients with prostate cancer and diabetes. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 6, 2017 Category: Endocrinology Source Type: research

Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos ® on parasympathetic tone and hepatic energy metabolism
Conclusion Non-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

PGC-1 α functions as a co-suppressor of XBP1s to regulate glucose metabolism
Conclusions Our findings reveal a novel function of PGC-1α as a suppressor of XBP1s function, suggesting that hepatic PGC-1α promotes gluconeogenesis through multiple pathways as a co-activator for HNF4α and FoxO1 and also as a suppressor for anti-gluconeogenic transcription factor XBP1s. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Optimal housing temperatures for mice to mimic the thermal environment of humans: An  experimental study
Conclusions We show that housing mice at thermoneutrality is an advantageous step towards aligning mouse energy metabolism to human energy metabolism. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Dual role of protein tyrosine phosphatase 1B in the progression and reversion of non-alcoholic steatohepatitis
Conclusions PTP1B elicits a dual role in NASH progression and reversion. Additionally, our results support a new role for PTP1B in oval cell proliferation during NAFLD. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance
Conclusions Our studies have unveiled a fascinating interaction between elevated NAMPT activity in skeletal muscle and voluntary exercise that was manifest as a striking improvement in exercise endurance. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha
Conclusions These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis
Conclusions Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for the first time the distinct and region-specific functions of CART in controlling feeding and energy homeostasis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats
Conclusion Our results highlight a key role of hypothalamic de novo ceramide synthesis in central insulin resistance installation and glucose homeostasis dysregulation associated with obesity. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Neurturin is a PGC-1 α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation
Conclusions Our findings indicate that neurturin is a mediator of PGC-1α1-dependent retrograde signaling from muscle to motor neurons. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Macrophages sensing oxidized DAMPs reprogram their metabolism to support redox homeostasis and inflammation through a TLR2-Syk-ceramide dependent mechanism
Conclusions Together, these data demonstrate the metabolic and bioenergetic requirements that enable macrophages to translate tissue oxidation status into either antioxidant or inflammatory responses via sensing OxPL. Targeting dysregulated redox homeostasis in macrophages could therefore lead to novel therapies to treat chronic inflammation. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase
Conclusions Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing
Conclusion Mitochondrial long chain fatty acid β-oxidation is critical for the maintenance of the brown adipocyte phenotype both during times of activation and quiescence. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells
Conclusions FFA1 and GPBAR1 activation individually increased electrical activity in L-cells by recruiting pathways that include activation of TRPC3 and L-type voltage-gated Ca2+ channels. Synergy between the pathways activated downstream of these receptors was observed both at the level of Ca2+ elevation and GLP-1 secretion. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes
Conclusions VPS13C is present on BA LDs where is targeted to a distinct subdomain. VPS13C limits the access of ATGL to LD and loss of VPS13C elevates lipolysis and promotes oxidative gene expression. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Targeting erythropoietin protects against proteinuria in type 2 diabetic patients and in zebrafish
Conclusions EPO was identified as a direct renal protective factor, promoting renal embryonic development and protecting kidneys from hyperglycemia induced nephropathy. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Adiponectin release and insulin receptor targeting share trans-Golgi-dependent endosomal trafficking routes
Conclusions Our findings suggest that adiponectin secretion and insulin receptor surface targeting utilize the same post-Golgi trafficking pathways that are essential for an appropriate systemic insulin sensitivity and glucose homeostasis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Cadm2 regulates body weight and energy homeostasis in mice
Conclusions Together these data illustrate that reducing Cadm2 expression can reverse several traits associated with the metabolic syndrome including obesity, insulin resistance, and impaired glucose homeostasis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Mitochondrial fission is associated with UCP1 activity in human brite/beige adipocytes
Conclusion Our data demonstrate that white-to-brite conversion of human adipocytes relies on molecular, morphological and functional changes in mitochondria, which enable brite/beige cells to carry out thermogenesis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Amylin – Its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity
Conclusion We propose here that the effects of amylin may be homeostatic and hedonic in nature. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Desacetyl- α-melanocyte stimulating hormone and α-melanocyte stimulating hormone are required to regulate energy balance
Conclusions Based on these data we propose that there is potential to exploit the naturally occurring POMC-derived peptides to treat obesity but this relies on first understanding the specific function(s) for desacetyl-α-MSH and α-MSH. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Cdkn2a deficiency promotes adipose tissue browning
Conclusion Our results offer novel insight into brown/beige adipocyte functions, which has recently emerged as an attractive therapeutic strategy for obesity and T2D. Modulating Cdkn2a-regulated signaling cascades may be of interest for the treatment of metabolic disorders. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice
Conclusion Our results support a role of increased lactate uptake in hepatocytes during HFD that, in turn, induce a metabolic shift stimulating SREBP1 activity and lipid accumulation. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal
Conclusion In summary, mitophagy may be enhanced in endurance-trained runners based on elevated markers of mitophagy and mitochondrial dynamics. The HFM did not alter autophagy or mitophagy in either group. The absence of a relationship between mitophagy markers and metabolic flexibility suggests that mitophagy is not a key determinant of metabolic flexibility in a healthy population, but further investigation is warranted. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation
Conclusion These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

A polyphenol-rich cranberry extract reverses insulin resistance and hepatic steatosis independently of body weight loss
Conclusions Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols. (Source: Molecular Metabolism)
Source: Molecular Metabolism - December 3, 2017 Category: Endocrinology Source Type: research

Induction of fibroblast growth factor 21 does not require activation of the hepatic X-box binding protein 1 in mice
Conclusion Hepatic Xbp1 is not required for induction of FGF21 under physiologic or pathophysiologic conditions in vivo. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 6, 2017 Category: Endocrinology Source Type: research

Modulation of cognition and anxiety-like behavior by bone remodeling
Conclusions These results indicate that bone remodeling is a determinant of brain function. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 6, 2017 Category: Endocrinology Source Type: research

Receptor Structure-Based Discovery of Non-metabolite Agonists for the Succinate Receptor GPR91
Conclusions These novel, synthetic non-metabolite GPR91 agonists will be valuable both as pharmacological tools to delineate the GPR91-mediated functions of succinate and as leads for the development of GPR91-targeted drugs to potentially treat low grade metabolic inflammation and diabetic complications such as retinopathy and nephropathy. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 30, 2017 Category: Endocrinology Source Type: research

KLK5 induces shedding of DPP4 from circulatory Th17 cells in Type 2 Diabetes
Conclusions Our study provides mechanistic insights into the molecular interaction between KLK5 and DPP4 as well as CD4+ T cell derived KLK5 mediated enzymatic cleavage of DPP4 from cell surface. Thus, our study uncovers a hitherto unknown cellular source and mechanism behind enhanced plasma DPP4 activity in T2DM. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 28, 2017 Category: Endocrinology Source Type: research

Host –microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice
Conclusions Our results provide new insights on host–microbiota interaction during colonization of GF mice and the resulting effects on adiposity and glucose metabolism in a time resolved fashion. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 25, 2017 Category: Endocrinology Source Type: research

Host-microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice
Conclusions Our results provide new insights on host-microbiota interaction during colonization of GF mice and the resulting effects on adiposity and glucose metabolism in a time resolved fashion. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 21, 2017 Category: Endocrinology Source Type: research

FGF21 mimetic antibody stimulates UCP1-independent brown fat thermogenesis via FGFR1/ βKlotho complex in non-adipocytes
Conclusions Collectively, we propose that FGFR1/βKlotho targeted therapy indeed mimics the action of FGF21 in vivo and stimulates UCP1-independent brown fat thermogenesis through receptors outside of adipocytes and likely in the nervous system. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 19, 2017 Category: Endocrinology Source Type: research

The Mitochondrial Pyruvate Carrier Mediates High Fat Diet-Induced Increases in Hepatic TCA Cycle Capacity
Conclusions By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 19, 2017 Category: Endocrinology Source Type: research

Bombesin-like receptor 3 (Brs3) expression in glutamatergic, but not GABAergic, neurons is required for regulation of energy metabolism
Conclusions Brs3 expression in glutamatergic neurons is both necessary and sufficient for full Brs3 function in energy metabolism. In these experiments, no function was identified for Brs3 in GABAergic neurons. The data suggest that the anti-obesity pharmacologic actions of BRS-3 agonists occur via agonism of receptors on glutamatergic neurons. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 15, 2017 Category: Endocrinology Source Type: research

Superior reductions in hepatic steatosis and fibrosis with co-administration of a glucagon-like peptide-1 receptor agonist and obeticholic acid in mice
Conclusion Our data suggest a complementary or synergistic therapeutic effect of GLP-1R and FXR agonism in mouse models of metabolic disease and NASH. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 14, 2017 Category: Endocrinology Source Type: research

Amino Acid Sensing in Hypothalamic Tanycytes via Umami Taste Receptors
Conclusion Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 14, 2017 Category: Endocrinology Source Type: research

The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice
Conclusions GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 4, 2017 Category: Endocrinology Source Type: research

The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans
Conclusions Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (patho)physiologically involved in fructose metabolism and metabolic health. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 4, 2017 Category: Endocrinology Source Type: research

Decreasing CB1 receptor signaling in Kupffer cells improves insulin sensitivity in obese mice
Conclusion These findings suggest that CB1R expressed in KCs plays a critical role in obesity-related hepatic insulin resistance via a pro-inflammatory mechanism. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 2, 2017 Category: Endocrinology Source Type: research

An unbiased silencing screen in muscle cells identifies miR-320a, miR-150, miR-196b, and miR-34c as regulators of skeletal muscle mitochondrial metabolism
Conclusion The results show that that microRNA-320a, microRNA-196b-3p, microRNA-150-5p, and microRNA-34c-3p are tightly related to in vivo skeletal muscle mitochondrial function in humans and identify these microRNAs as targets for improving mitochondrial metabolism. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 1, 2017 Category: Endocrinology Source Type: research

Acute Activation of GLP-1-expressing Neurons Promotes Glucose Homeostasis and Insulin Sensitivity
Conclusions We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 1, 2017 Category: Endocrinology Source Type: research

GLP-1 does not increase heart rate in a heart autonomous manner The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice
Conclusions GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner. Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 1, 2017 Category: Endocrinology Source Type: research

Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants
CONCLUSIONS These data suggest that greater infant adiposity is associated with suppressed AMPK activity and reduced lipid oxidation in MSCs from infants born to mothers with obesity and may be an important, early marker of underlying obesity risk. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 1, 2017 Category: Endocrinology Source Type: research

Absence of the kinase S6k1 mimics the effect of chronic endurance exercise on glucose tolerance and muscle oxidative stress
Conclusion In high-fat fed mice, loss of S6K1 mimics endurance exercise training by reducing mitochondrial ROS production and upregulating oxidative utilization of ketone bodies. Pharmacological targeting of S6K1 may improve the outcome of exercise-based interventions in obesity and diabetes. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 26, 2017 Category: Endocrinology Source Type: research

Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety
Conclusions OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 24, 2017 Category: Endocrinology Source Type: research

Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury
Conclusions Acute or binge ethanol consumption significantly increases circulating FGF21 levels in both humans and mice. However, FGF21 does not play a role in acute ethanol clearance. In contrast, chronic ethanol consumption in the absence of FGF21 is associated with significant liver pathology alone or in combination with excess mortality, depending on the type of diet consumed with ethanol. This suggests that FGF21 protects against long term ethanol induced hepatic damage and may attenuate progression of alcoholic liver disease. Further study is required to assess the therapeutic potential of FGF21 in the treatment of a...
Source: Molecular Metabolism - August 20, 2017 Category: Endocrinology Source Type: research