A Novel Mechanism for Th17 Inflammation in Human Type 2 Diabetes Mellitus.
Abstract In their recent study, Nicholas et al. challenge the current dogma that T cell inflammation must be fueled by glycolysis and demonstrate a novel metabolic mechanism for Th17 inflammation in human type 2 diabetes mellitus (T2DM): a combination of increased environmental long-chain fatty acid metabolites coupled with decreased fatty acid oxidation. PMID: 31767267 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - November 22, 2019 Category: Endocrinology Authors: Kiernan K, MacIver NJ Tags: Trends Endocrinol Metab Source Type: research

Methylglyoxal Metabolism and Aging-Related Disease: Moving from Correlation toward Causation.
Abstract Methylglyoxal (MG) is a ubiquitous metabolite that spontaneously reacts with biopolymers forming advanced glycation end-products (AGEs). AGEs are strongly associated with aging-related diseases, including cancer, neurodegenerative diseases, and diabetes. As the formation of AGEs is nonenzymatic, the damage caused by MG and AGEs has been regarded as unspecific. This may have resulted in the field generally been regarded as unappealing by many researchers, as detailed mechanisms have been difficult to probe. However, accumulating evidence highlighting the importance of MG in human metabolism and disease, as...
Source: Trends in Endocrinology and Metabolism: TEM - November 19, 2019 Category: Endocrinology Authors: Kold-Christensen R, Johannsen M Tags: Trends Endocrinol Metab Source Type: research

Diet-Induced Modification of the Sperm Epigenome Programs Metabolism and Behavior.
Abstract Globally, obesity has reached epidemic proportions. The rapidly increasing numbers of overweight people can be traced back to overconsumption of energy-dense, poor-quality foods as well as physical inactivity. This development has far-reaching and costly implications. Not only is obesity associated with serious physiological and psychological complications, but mounting evidence also indicates a ripple effect through generations via epigenetic changes. Parental obesity could induce intergenerational and transgenerational changes in metabolic and brain function of the offspring. Most research has focused o...
Source: Trends in Endocrinology and Metabolism: TEM - November 16, 2019 Category: Endocrinology Authors: Bodden C, Hannan AJ, Reichelt AC Tags: Trends Endocrinol Metab Source Type: research

Immunoregulatory Functions of Nuclear Receptors: Mechanisms and Therapeutic Implications.
ou S Abstract Members of the nuclear receptor superfamily serve as master regulators in signaling by either positively or negatively regulating gene expression. Accumulating evidence has suggested that nuclear receptors are actively involved in immune responses, with specific roles in different immune cell compartments that contribute to both normal function and to disease development. The druggable properties of nuclear receptors have made them ideal modulatory therapeutic targets. Here, we revisit nuclear receptor biology, summarize recent advances in our understanding of the immunological functions of nuclear r...
Source: Trends in Endocrinology and Metabolism: TEM - November 6, 2019 Category: Endocrinology Authors: Zhao L, Gimple RC, Yang Z, Wei Y, Gustafsson JÅ, Zhou S Tags: Trends Endocrinol Metab Source Type: research

Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology.
Abstract Autophagy contributes to cellular quality control and energetics through lysosomal breakdown and recycling of essential cellular components. Chaperone-mediated autophagy (CMA) adds to these autophagic functions the ability to timely and selectively degrade single tagged proteins to terminate their cellular function and, in this way, participate in the regulation of multiple cellular processes. Many cancer cells upregulate CMA for protumorigenic and prosurvival purposes. However, growing evidence supports a physiological role for CMA in limiting malignant transformation. Understanding the mechanisms behind...
Source: Trends in Endocrinology and Metabolism: TEM - November 4, 2019 Category: Endocrinology Authors: Arias E, Cuervo AM Tags: Trends Endocrinol Metab Source Type: research

Growth Factor-Dependent and -Independent Activation of mTORC2.
Abstract The target of rapamycin complex 2 (TORC2) was discovered in 2002 in budding yeast. Its mammalian counterpart, mTORC2, was first described in 2004. Soon thereafter it was demonstrated that mTORC2 directly phosphorylates Akt on Ser473, ending a long search for the elusive 'second' insulin-responsive Akt kinase. In this review we discuss key evidence pertaining to the subcellular localization of mTORC2, highlighting a spatial heterogeneity that relates to mTORC2 activation. We summarize current models for how growth factors (GFs), such as insulin, trigger mTORC2 activation, and we provide a comprehensive dis...
Source: Trends in Endocrinology and Metabolism: TEM - November 4, 2019 Category: Endocrinology Authors: Knudsen JR, Fritzen AM, James DE, Jensen TE, Kleinert M, Richter EA Tags: Trends Endocrinol Metab Source Type: research

Role of Nitric Oxide in Insulin Secretion and Glucose Metabolism.
Abstract Nitric oxide (NO) contributes to carbohydrate metabolism and decreased NO bioavailability is involved in the development of type 2 diabetes mellitus (T2DM). NO donors may improve insulin signaling and glucose homeostasis in T2DM and insulin resistance (IR), suggesting the potential clinical importance of NO-based interventions. In this review, site-specific roles of the NO synthase (NOS)-NO pathway in carbohydrate metabolism are discussed. In addition, the metabolic effects of physiological low levels of NO produced by constitutive NOS (cNOS) versus pathological high levels of NO produced by inducible NOS...
Source: Trends in Endocrinology and Metabolism: TEM - November 2, 2019 Category: Endocrinology Authors: Bahadoran Z, Mirmiran P, Ghasemi A Tags: Trends Endocrinol Metab Source Type: research

Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism.
Abstract The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiology and metabolism. However, the mechanisms that underlie these observations remain largely unknown. Recent findings have implicated microbially derived mediators as potential signals between the gut microbiome and host circadian clocks; two specific mediators are discussed in this review: short-chain fatty acids (SCFAs) and...
Source: Trends in Endocrinology and Metabolism: TEM - October 30, 2019 Category: Endocrinology Authors: Frazier K, Chang EB Tags: Trends Endocrinol Metab Source Type: research

Polymeric Carriers for Controlled Drug Delivery in Obesity Treatment.
Abstract The global rise in the prevalence of obesity and affiliated metabolic syndrome poses a significant threat to human health. Various approaches, including bariatric surgery and pharmacotherapy, have been used in the clinical setting for obesity treatment; however, these conventional options remain ineffective and carry risks of adverse effects. Therefore, treatments with higher efficacy and specificity are urgently required. Emerging drug delivery systems use polymeric materials and chemical strategies to improve therapeutic efficacy and specificity through stabilization and spatiotemporally controlled rele...
Source: Trends in Endocrinology and Metabolism: TEM - October 25, 2019 Category: Endocrinology Authors: Huang D, Deng M, Kuang S Tags: Trends Endocrinol Metab Source Type: research

Energy Trade-offs in Host Defense: Immunology Meets Physiology.
Abstract Host defense relies not only on microbicidal mechanisms (resistance), but also on management of collateral damage (tolerance). Here, we discuss how this immunology concept converges with a physiology-born theory on the dichotomy of thermometabolic responses in infection (fever versus hypothermia), yielding a model of immunity that transcends discipline barriers. PMID: 31668960 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - October 25, 2019 Category: Endocrinology Authors: Steiner AA, Romanovsky AA Tags: Trends Endocrinol Metab Source Type: research

TEM at 30: Advancing Topics in Endocrinology.
PMID: 31668961 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - October 24, 2019 Category: Endocrinology Authors: Beymer M Tags: Trends Endocrinol Metab Source Type: research

Endocrine Regulations in Human-Dog Coexistence through Domestication.
Abstract Endocrine system regulation is important for the maintenance of homeostasis; it controls hormonal functions in complex physiology and behavior and adaptations to social environments. Evidence indicates that for more than 35 000 years, dogs (Canis familiaris) have been domesticated through living with humans. For example, they have acquired human-like social skills, such as eye gazing and pointing gestures. These unique behaviors are, at least partially, regulated by hormones and are thought to have been genetically altered throughout domestication. Glucocorticoids affect social tolerance, while oxytocin f...
Source: Trends in Endocrinology and Metabolism: TEM - October 23, 2019 Category: Endocrinology Authors: Kikusui T, Nagasawa M, Nomoto K, Kuse-Arata S, Mogi K Tags: Trends Endocrinol Metab Source Type: research

A Tale of Two Proteins: Betaglycan, IGSF1, and the Continuing Search for the Inhibin B Receptor.
é E Abstract Inhibins are gonadal hormones that suppress follicle-stimulating hormone (FSH) synthesis by pituitary gonadotrope cells. The structurally related activins stimulate FSH by signaling through complexes of type I and type II receptors. Two models of inhibin action were proposed in 2000. First, inhibins function as competitive receptor antagonists, binding activin type II receptors with high affinity in the presence of the TGF-β type III coreceptor, betaglycan. Second, immunoglobulin superfamily, member 1 (IGSF1, then called p120) was proposed to mediate inhibin B antagonism of activin signali...
Source: Trends in Endocrinology and Metabolism: TEM - October 22, 2019 Category: Endocrinology Authors: Bernard DJ, Smith CL, Brûlé E Tags: Trends Endocrinol Metab Source Type: research

A Metabolic Perspective on Reward Abnormalities in Anorexia Nervosa.
Abstract Anorexia nervosa (AN) is the psychiatric disorder with the highest mortality rate; however, the mechanisms responsible for its pathogenesis remain largely unknown. Large-scale genome-wide association studies (GWAS) have identified genetic loci associated with metabolic features in AN. Metabolic alterations that occur in AN have been mostly considered as consequences of the chronic undernutrition state but until recently have not been linked to the etiology of the disorder. We review the molecular basis of AN based on human genetics, with an emphasis on the molecular components controlling energy homeostas...
Source: Trends in Endocrinology and Metabolism: TEM - October 21, 2019 Category: Endocrinology Authors: Duriez P, Ramoz N, Gorwood P, Viltart O, Tolle V Tags: Trends Endocrinol Metab Source Type: research

What Is GLP-1 Really Doing in Obesity?
Abstract Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released in response to meal ingestion and enhances insulin secretion from pancreatic β cells. In several human studies, GLP-1 secretory responses to oral glucose load or a meal were decreased in subjects with obesity, glucose intolerance, or diabetes compared with those in healthy subjects. However, the results of meta-analysis and cohort studies do not necessarily support this concept. Results from animal studies are also inconsistent; in multiple studies, GLP-1 secretory responses to a meal were repeatedly higher in diet-induced obese r...
Source: Trends in Endocrinology and Metabolism: TEM - October 18, 2019 Category: Endocrinology Authors: Hira T, Pinyo J, Hara H Tags: Trends Endocrinol Metab Source Type: research

Ghrelin Signaling: GOAT and GHS-R1a Take a LEAP in Complexity.
Abstract Ghrelin and the growth hormone secretagogue receptor 1a (GHS-R1a) are important targets for disorders related to energy balance and metabolic regulation. Pharmacological control of ghrelin signaling is a promising avenue to address health issues involving appetite, weight gain, obesity, and related metabolic disorders, and may be an option for patients suffering from wasting conditions like cachexia. In this review, we summarize recent developments in the biochemistry of ghrelin and GHS-R1a signaling. These include unravelling the enzymatic transformations that generate active ghrelin and the discovery of...
Source: Trends in Endocrinology and Metabolism: TEM - October 18, 2019 Category: Endocrinology Authors: Abizaid A, Hougland JL Tags: Trends Endocrinol Metab Source Type: research

NAFLD and Atherosclerosis: Two Sides of the Same Dysmetabolic Coin?
om AG Abstract The prevalence of non-alcoholic fatty liver disease (NAFLD) is strongly increasing and may put patients at increased risk for atherosclerotic cardiovascular disease (asCVD). Both disease phenotypes often co-occur, in the case of obesity, insulin resistance, diabetes mellitus type 2, and the metabolic syndrome. We explore the pathogenesis of NAFLD, the epidemiology of asCVD in NAFLD patients, shared drivers of both phenotypes, and factors caused by NAFLD that contribute to asCVD. Genetic studies support that NAFLD may drive asCVD through mixed hyperlipidemia. Next, we discuss the prospects of lifesty...
Source: Trends in Endocrinology and Metabolism: TEM - October 17, 2019 Category: Endocrinology Authors: Stols-Gonçalves D, Hovingh GK, Nieuwdorp M, Holleboom AG Tags: Trends Endocrinol Metab Source Type: research

Neuronal Cell Cycle Events Link Caloric Intake to Obesity.
Abstract Obesity is a neurological disorder that operates by favoring energy storage within adipose depots and increased caloric intake. Most cases of human obesity are acquired without any underlying genetic basis. Here, we suggest that obesity can impair the function of some hypothalamic neurons critical to body weight regulation. Genetic ablation of the retinoblastoma (Rb) gene within pro-opiomelanocortin (POMC) neurons leads to death of the neurons and subsequent obesity. The Rb protein (pRb), a key inhibitor of the cell cycle, can also be inactivated by cyclin dependent kinase (CDK)-mediated phosphorylation. ...
Source: Trends in Endocrinology and Metabolism: TEM - October 16, 2019 Category: Endocrinology Authors: Iqbal N, Zhu L, Chua SC Tags: Trends Endocrinol Metab Source Type: research

The Complexity of Making Ubiquinone.
Abstract Ubiquinone (UQ, coenzyme Q) is an essential electron transfer lipid in the mitochondrial respiratory chain. It is a main source of mitochondrial reactive oxygen species (ROS) but also has antioxidant properties. This mix of characteristics is why ubiquinone supplementation is considered a potential therapy for many diseases involving mitochondrial dysfunction. Mutations in the ubiquinone biosynthetic pathway are increasingly being identified in patients. Furthermore, secondary ubiquinone deficiency is a common finding associated with mitochondrial disorders and might exacerbate these conditions. Recent de...
Source: Trends in Endocrinology and Metabolism: TEM - October 7, 2019 Category: Endocrinology Authors: Wang Y, Hekimi S Tags: Trends Endocrinol Metab Source Type: research

Natural Killer Cells as Sensors of Adipose Tissue Stress.
ström NK Abstract Adipose tissue macrophages (ATMs) orchestrate low-grade chronic adipose tissue inflammation, linking obesity and insulin resistance. Whereas factors contributing to macrophage accumulation in adipose tissue are established, little is known regarding signals that link adipocyte stress to proinflammatory activation of macrophages. Natural killer (NK) cells are specialized innate lymphocytes that identify and respond to stressed cells. In this Opinion, we discuss the possibility of NK cells to function as sensors recognizing adipose tissue stress. We further summarize recent literature suggesti...
Source: Trends in Endocrinology and Metabolism: TEM - October 6, 2019 Category: Endocrinology Authors: Fernø J, Strand K, Mellgren G, Stiglund N, Björkström NK Tags: Trends Endocrinol Metab Source Type: research

Emerging Molecular Targets for Treatment of Nonalcoholic Fatty Liver Disease.
Abstract In parallel with the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide. Disequilibrium of lipid metabolism and the subsequent metabolic-stress-induced inflammation are believed to be central in the pathogenesis of NAFLD. Of note, metabolic inflammation is primarily mediated by innate immune signaling, which is increasingly recognized as a driving force in NAFLD progression. Currently, a series of agents targeting one or more of these pathomechanisms have shown encouraging results in preclinical models and clinical trials. This review ...
Source: Trends in Endocrinology and Metabolism: TEM - October 6, 2019 Category: Endocrinology Authors: Chen Z, Yu Y, Cai J, Li H Tags: Trends Endocrinol Metab Source Type: research

Clinical/Translational Aspects of Advanced Glycation End-Products.
Abstract Advanced glycation end-products (AGEs) have been implicated in chronic hyperglycemia and age-related diseases. Endogenous AGEs produced by humans generate oxidative stress and activation of inflammatory signaling pathways via AGE-specific receptors. The present review summarizes current knowledge on the pathogenic role of AGEs in chronic noncommunicable diseases. Although correlations exist between glycation and the pathogenesis of these diseases, uncertainties remain in light of recurrent intervention failures of apparently promising animal models to be translated into clinically useful anti-AGE str...
Source: Trends in Endocrinology and Metabolism: TEM - October 6, 2019 Category: Endocrinology Authors: Zeng C, Li Y, Ma J, Niu L, Tay FR Tags: Trends Endocrinol Metab Source Type: research

Hormesis in Health and Chronic Diseases.
Abstract 'What doesn't kill you makes you stronger'. Hormesis, the paradoxical beneficial effects of low-dose stressors, can be better defined as the biphasic dose-effect or time-effect relationship for any substance. Here we review hormesis-like phenomena in the context of chronic diseases for many substances, including lifestyle factors and endocrine factors. Intermittent or pulsatile exposure can generate opposite effects compared with continuous exposure. An initial exposure can elicit an adaptive stress response with long-lasting protection against subsequent exposures. Early-life stress can increase resilien...
Source: Trends in Endocrinology and Metabolism: TEM - September 11, 2019 Category: Endocrinology Authors: Li X, Yang T, Sun Z Tags: Trends Endocrinol Metab Source Type: research

Maternal Microbiome and Metabolic Health Program Microbiome Development and Health of the Offspring.
Abstract Maternal nutritional, metabolic, and physiological states, as well as exposure to various environmental factors during conception, gestation, and lactation, have a fundamental role in the health programming of the offspring. Therefore, alterations affecting the maternal microbiota might indirectly influence fetal development. In addition, such alterations could be transmitted to the progeny at different stages of infant development (e.g., preconception, prenatal, or postnatal), thereby favoring the development of an altered microbiota in the neonate. Microbial changes of this kind have been linked to an i...
Source: Trends in Endocrinology and Metabolism: TEM - September 4, 2019 Category: Endocrinology Authors: Calatayud M, Koren O, Collado MC Tags: Trends Endocrinol Metab Source Type: research

Hypothalamic Heuristics for Survival.
Abstract Hypothalamic neurons implicated in energy homeostasis (Agrp, POMC, orexin, MCH) display fast, nutrient-independent dynamics. They do not simply mirror the slowly changing internal nutrient levels, but adapt rapidly to diverse external cues. Moreover, instead of eating, neonatal Agrp cells stimulate mother-attracting vocalisations, illustrating heuristic energy control beyond nutrient sensing or dietary self-control. PMID: 31492605 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - September 3, 2019 Category: Endocrinology Authors: Burdakov D, Peleg-Raibstein D Tags: Trends Endocrinol Metab Source Type: research

The FoxO-Autophagy Axis in Health and Disease.
Abstract Autophagy controls cellular remodeling and quality control. Dysregulated autophagy has been implicated in several human diseases including obesity, diabetes, cardiovascular disease, neurodegenerative diseases, and cancer. Current evidence has revealed that FoxO (forkhead box class O) transcription factors have a multifaceted role in autophagy regulation and dysregulation. Nuclear FoxOs transactivate genes that control the formation of autophagosomes and their fusion with lysosomes. Independently of transactivation, cytosolic FoxO proteins induce autophagy by directly interacting with autophagy proteins. A...
Source: Trends in Endocrinology and Metabolism: TEM - August 26, 2019 Category: Endocrinology Authors: Cheng Z Tags: Trends Endocrinol Metab Source Type: research

Impact of Circadian Disruption on Cardiovascular Function and Disease.
Abstract The circadian system, that is ubiquitous across species, generates ~24 h rhythms in virtually all biological processes, and allows them to anticipate and adapt to the 24 h day/night cycle, thus ensuring optimal physiological function. Epidemiological studies show time-of-day variations in adverse cardiovascular (CV) events, and controlled laboratory studies demonstrate a circadian influence on key markers of CV function and risk. Furthermore, circadian misalignment, that is typically experienced by shift workers as well as by individuals who experience late eating, (social) jet lag, or circadian rhythm sl...
Source: Trends in Endocrinology and Metabolism: TEM - August 16, 2019 Category: Endocrinology Authors: Chellappa SL, Vujovic N, Williams JS, Scheer FAJL Tags: Trends Endocrinol Metab Source Type: research

Lipid Regulators of Thermogenic Fat Activation.
Abstract The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy expenditure represents one such approach. Brown adipocytes and the related beige adipocytes oxidize fatty acids and glucose to generate heat and are activated by cold exposure or consumption of high-calorie diets. Alternative, more practical means to activate thermogenic fat are needed. Here, we review emerging data suggesting new roles for lipids in activating thermogenesis that extend beyond their serving as a fuel source for heat generation. Lipi...
Source: Trends in Endocrinology and Metabolism: TEM - August 16, 2019 Category: Endocrinology Authors: Park H, He A, Lodhi IJ Tags: Trends Endocrinol Metab Source Type: research

Are Lifestyle Therapies Effective for NAFLD Treatment?
Abstract Nonalcoholic fatty liver disease (NAFLD) is becoming the most common liver disorder worldwide. Specifically, nonalcoholic steatohepatitis (NASH) and fibrosis pose an enormous burden for patients and health-care systems. In the absence of approved pharmacological therapies, effective lifestyle interventions for NAFLD, such as dietary strategies and exercise training, are currently the therapeutic strategies of choice. This review covers the influence of macronutrient quality and quantity (i.e., low-carbohydrate and high-protein diets), for successful reduction of intrahepatocellular lipids (IHL). Moreover,...
Source: Trends in Endocrinology and Metabolism: TEM - August 15, 2019 Category: Endocrinology Authors: El-Agroudy NN, Kurzbach A, Rodionov RN, O'Sullivan J, Roden M, Birkenfeld AL, Pesta DH Tags: Trends Endocrinol Metab Source Type: research

Handling Parathormone Receptor Type 1 in Skeletal Diseases: Realities and Expectations of Abaloparatide.
Gortazar AR Abstract Musculoskeletal disorders represent an elevated socioeconomic burden for developed aging societies. Osteoporosis (OP) has been treated with antiresorptive therapies or with teriparatide that was until recently the only anabolic therapy. However, approval of osteoporosis treatment in postmenopausal women with abaloparatide, which is an analog of parathyroid hormone-related peptide (PTHrP), has created a new alternative for OP management. The success of this new treatment is related to differential mechanisms of activation of PTH receptor type 1 (PTH1R) by abaloparatide and PTH. Here, we address...
Source: Trends in Endocrinology and Metabolism: TEM - August 11, 2019 Category: Endocrinology Authors: Ardura JA, Portal-Núñez S, Alonso V, Bravo B, Gortazar AR Tags: Trends Endocrinol Metab Source Type: research

Metformin as Anti-Aging Therapy: Is It for Everyone?
Abstract Metformin is the most widely prescribed oral hypoglycemic medication for type 2 diabetes worldwide. Metformin also retards aging in model organisms and reduces the incidence of aging-related diseases such as neurodegenerative disease and cancer in humans. In spite of its widespread use, the mechanisms by which metformin exerts favorable effects on aging remain largely unknown. Further, not all individuals prescribed metformin derive the same benefit and some develop side effects. Before metformin finds its way to mainstay therapy for anti-aging, a more granular understanding of the effects of the drug in ...
Source: Trends in Endocrinology and Metabolism: TEM - August 9, 2019 Category: Endocrinology Authors: Soukas AA, Hao H, Wu L Tags: Trends Endocrinol Metab Source Type: research

Neuron-Astrocyte Liaison to Maintain Lipid Metabolism of Brain.
Abstract Neuron-astrocyte crosstalk is a tightly regulated process that is essential for overall proper functioning of the brain. Maria S. Ioannou et al. (Cell, 2019) revealed a novel and compelling function of neuron-astrocyte crosstalk that explains how neurons cope with their accumulating toxic lipid particles under various scenarios. PMID: 31401016 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - August 8, 2019 Category: Endocrinology Authors: Mukherjee S, Suresh SN Tags: Trends Endocrinol Metab Source Type: research

Heterogeneity and Similarities in GLP-1 Receptor Agonist Cardiovascular Outcomes Trials.
Abstract The latest recommendations from the American Diabetes Association and the European Association for the Study of Diabetes prioritize the use of drugs with proven cardiovascular (CV) benefit in patients with established CV disease. Especially among the glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RA) class, results of cardiovascular outcomes trials (CVOT) have been heterogeneous. Baseline characteristics of the population, study design, drugs in the control arm, modifications of CV risk factors, including glycemic control, reduction of hypoglycemia, and the GLP-1RA direct effects on CV cells and ti...
Source: Trends in Endocrinology and Metabolism: TEM - August 7, 2019 Category: Endocrinology Authors: Caruso I, Cignarelli A, Giorgino F Tags: Trends Endocrinol Metab Source Type: research

A Possible Neurodegeneration Mechanism Triggered by Diabetes.
Abstract Several conditions result in neurodegeneration; among which diabetes mellitus (DM) is of crucial importance. Tau (τ) malfunction is a major pathological process participating in neurodegeneration. Despite extensive considerations, the actual causative link between DM and τ abnormalities remains uncertain thus far. Phosphorylated (p)-τ at Thr-Pro motifs can exist in the two distinct cis and trans conformations. cis is neurotoxic, and is accumulated upon various stress conditions, such as nutrition depletion. We assume that pathogenic cis p-τ is the central mediator of neurodegeneration in D...
Source: Trends in Endocrinology and Metabolism: TEM - August 7, 2019 Category: Endocrinology Authors: Farhadi A, Vosough M, Zhang JS, Tahamtani Y, Shahpasand K Tags: Trends Endocrinol Metab Source Type: research

Huntington's Disease: Astrocytes Shift to Fatty Acid Metabolism.
Abstract A recent study by Polyzos et al. (Cell Metab., 2019) shows that astrocytes in a Huntington disease (HD) mouse model switch from glycolysis to fatty acid oxidation (FAO), causing increased superoxide radical anion production and loss of succinate dehydrogenase (SD) activity. Blocking mitochondria reactive oxygen species (ROS) with an antioxidant compound called XJB-5-151 reversed lipofuscin formation and protected the mice. PMID: 31399292 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - August 6, 2019 Category: Endocrinology Authors: Van Houten B Tags: Trends Endocrinol Metab Source Type: research

Insights on Obesity in Children and Adults: Individualizing Management.
Abstract For the management of obesity in childhood and adolescence, nonoperative approaches have limited efficacy, including community-based and behavioral interventions and pharmacotherapy approved for use in adults. Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy are efficacious in reducing weight, body mass index, and comorbidities in adolescents. Understanding the phenotype associated with obesity provides an opportunity to individualize patients' treatments directed at the brain-gut axis. These phenotypes include rapid gastric emptying, increased fasting gastric volume, reduced postprandi...
Source: Trends in Endocrinology and Metabolism: TEM - August 5, 2019 Category: Endocrinology Authors: Camilleri M, Staiano A Tags: Trends Endocrinol Metab Source Type: research

Efferocytosis and Atherosclerosis: Regulation of Phagocyte Function by MicroRNAs.
Abstract There is evidence of the critical role of efferocytosis, the clearance of apoptotic cells (ACs) by phagocytes, in vascular cell homeostasis and protection against atherosclerosis. Specific microRNAs (miRs) can regulate atherogenesis by controlling the accumulation of professional phagocytes (e.g., macrophages) and nonprofessional phagocytes (i.e., neighboring tissue cells with the ability to acquire a macrophage-like phenotype) within the arterial wall, the differentiation of phagocytes into foam cells, the efferocytosis of apoptotic foam cells by phagocytes, and the phagocyte-mediated inflammatory respon...
Source: Trends in Endocrinology and Metabolism: TEM - August 2, 2019 Category: Endocrinology Authors: Tajbakhsh A, Bianconi V, Pirro M, Gheibi Hayat SM, Johnston TP, Sahebkar A Tags: Trends Endocrinol Metab Source Type: research

Reconstitution of Organismal Liver Clock Function Requires Light.
Abstract Recently Koronowski et al. (Cell, 2019) showed that reconstitution of the liver circadian clock in otherwise genetically arrhythmic mice revives the daily program of the nicotinamide adenine dinucleotide salvage pathway and glycogenesis in vivo. This liver-autonomous metabolic cycling cannot be sustained under constant darkness, revealing the importance of the daily light cycle to restore liver function. PMID: 31375394 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - July 31, 2019 Category: Endocrinology Authors: Miyake T, Doi M Tags: Trends Endocrinol Metab Source Type: research

Reassessing the Role of Diacylglycerols in Insulin Resistance.
Abstract Skeletal muscle (SM) insulin resistance (IR) plays an important role in the burden of obesity, particularly because it leads to glucose intolerance and type 2 diabetes. Among the mechanisms thought to link IR to obesity is the accumulation, in muscle cells, of different lipid metabolites. Diacylglycerols (DAGs) are subject of particular attention due to reported interactions with the insulin signaling cascade. Given that SM accounts for the majority of insulin-stimulated glucose uptake, this review integrates recent observational and mechanistic works with the sole focus on questioning the role of DAGs in...
Source: Trends in Endocrinology and Metabolism: TEM - July 30, 2019 Category: Endocrinology Authors: Jayasinghe SU, Tankeu AT, Amati F Tags: Trends Endocrinol Metab Source Type: research

Antagonism between Antiviral Signaling and Glycolysis.
Abstract RIG-I-like receptor (RLR)-mediated interferon production is critical for antiviral responses. A recent study (Zhang et al., Cell, 2019) uncovered a reciprocal inhibition between RLR signaling and glycolysis: lactate produced by glycolysis inhibits RLR signaling by binding to RLR signaling component mitochondrial antiviral-signaling (MAVS), whereas RLR activation suppresses glycolysis through inhibiting glycolysis enzyme hexokinase. PMID: 31349923 [PubMed - as supplied by publisher] (Source: Trends in Endocrinology and Metabolism: TEM)
Source: Trends in Endocrinology and Metabolism: TEM - July 23, 2019 Category: Endocrinology Authors: Chauhan AS, Zhuang L, Gan B Tags: Trends Endocrinol Metab Source Type: research

The Changing Clinical Spectrum of Hypophysitis.
Abstract Hypophysitis is a rare and potentially life-threatening disease, characterized by an elevated risk of complications, such as occurrence of acute central hypoadrenalism, persistent hypopituitarism, or extension of the inflammatory process to the neighboring neurological structures. In recent years, a large number of patients have been described as being affected by hypophysitis, due to the increased administration of immuno-chemotherapies. At the present time, the heterogeneous nature of hypophysitis diagnostic criteria and of the treatment protocols makes the management of affected patients difficult. We ...
Source: Trends in Endocrinology and Metabolism: TEM - July 22, 2019 Category: Endocrinology Authors: Chiloiro S, Capoluongo ED, Tartaglione T, Giampietro A, Bianchi A, Giustina A, Pontecorvi A, De Marinis L Tags: Trends Endocrinol Metab Source Type: research

Role of Diacylglycerol Kinases in Glucose and Energy Homeostasis.
Abstract Diacylglycerol kinases (DGKs) catalyze a reaction that converts diacylglycerol (DAG) to phosphatidic acid (PA). DAG and PA act as intermediates of de novo lipid synthesis, cellular membrane constituents, and signaling molecules. DGK isoforms regulate a variety of intracellular processes by terminating DAG signaling and activating PA-mediated pathways. The ten DGK isoforms are unique, not only structurally, but also in tissue-specific expression profiles, subcellular localization, regulatory mechanisms, and DAG preferences, suggesting isoform-specific functions. DAG accumulation has been associated with in...
Source: Trends in Endocrinology and Metabolism: TEM - July 19, 2019 Category: Endocrinology Authors: Massart J, Zierath JR Tags: Trends Endocrinol Metab Source Type: research

Epigenetics and Exercise.
Abstract Epigenetics can be defined as 'the structural adaptation of chromosomal regions so as to register, signal, or perpetuate altered activity states.' Increased transcription of key regulatory, metabolic, and myogenic genes is an early response to exercise and is important in mediating subsequent adaptations in skeletal muscle. DNA hypomethylation and histone hyperacetylation are emerging as important crucial events for increased transcription. The complex interactions between multiple epigenetic modifications and their regulation by metabolic changes and signaling events during exercise, with implications fo...
Source: Trends in Endocrinology and Metabolism: TEM - July 3, 2019 Category: Endocrinology Authors: McGee SL, Hargreaves M Tags: Trends Endocrinol Metab Source Type: research

Interactive and Multifactorial Mechanisms of Calcific Vascular and Valvular Disease.
Abstract Calcific vascular and valvular disease (CVVD) is widespread and has major health consequences. Although coronary artery calcification has long been associated with hyperlipidemia and increased mortality, recent evidence suggests that its progression is increased in association with cholesterol-lowering HMG-CoA reductase inhibitors ('statins') and long-term, high-intensity exercise. A nationwide trial showed no cardiovascular benefit of vitamin D supplements. Controversy remains as to whether calcium deposits in plaque promote or prevent plaque rupture. CVVD appears to occur through mechanisms similar to t...
Source: Trends in Endocrinology and Metabolism: TEM - July 3, 2019 Category: Endocrinology Authors: Demer LL, Tintut Y Tags: Trends Endocrinol Metab Source Type: research

Hexokinase-2 Glycolytic Overload in Diabetes and Ischemia-Reperfusion Injury.
Abstract Hexokinase-2 (HK2) was recently found to produce increased metabolic flux through glycolysis in hyperglycemia without concurrent transcriptional or other functional regulation. Rather, stabilization to proteolysis by increased glucose substrate binding produced unscheduled increased glucose metabolism in response to high cytosolic glucose concentration. This produces abnormal increases in glycolytic intermediates or glycolytic overload, driving cell dysfunction and vulnerability to the damaging effects of hyperglycemia in diabetes, explaining tissue-specific pathogenesis. Glycolytic overload is also activ...
Source: Trends in Endocrinology and Metabolism: TEM - June 23, 2019 Category: Endocrinology Authors: Rabbani N, Thornalley PJ Tags: Trends Endocrinol Metab Source Type: research

Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion.
Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion. Trends Endocrinol Metab. 2019 Jun 15;: Authors: Westermeier F, Holyoak T, Asenjo JL, Gatica R, Nualart F, Burbulis I, Bertinat R Abstract Pancreatic β-cells express the gluconeogenic enzymes glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBP), and phosphoenolpyruvate (PEP) carboxykinase (PCK), which modulate glucose-stimulated insulin secretion (GSIS) through their ability to reverse otherwise irreversible glycolytic steps. Here, we review current knowledge about the expression and regula...
Source: Trends in Endocrinology and Metabolism: TEM - June 15, 2019 Category: Endocrinology Authors: Westermeier F, Holyoak T, Asenjo JL, Gatica R, Nualart F, Burbulis I, Bertinat R Tags: Trends Endocrinol Metab Source Type: research

Nitro-Fatty Acid Logistics: Formation, Biodistribution, Signaling, and Pharmacology.
Abstract In addition to supporting cellular energetic demands and providing building blocks for lipid synthesis, fatty acids (FAs) are precursors of potent signaling molecules. In particular, the presence of conjugated double bonds on the fatty-acyl chain provides a preferential target for nitration generating nitro-FAs (NO2-FAs). The formation of NO2-FAs is a nonenzymatic process that requires reactive nitrogen species and occurs locally at the site of inflammation or during gastric acidification. NO2-FAs are electrophilic and display pleiotropic signaling actions through reversible protein alkylation. This revie...
Source: Trends in Endocrinology and Metabolism: TEM - June 10, 2019 Category: Endocrinology Authors: Schopfer FJ, Khoo NKH Tags: Trends Endocrinol Metab Source Type: research

Platelets as Potent Signaling Entities in Type 2 Diabetes Mellitus.
Abstract Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a dysregulated circulating inflammatory molecule tendency. T2DM is closely associated with systemic inflammation, endothelial dysfunction, cardiovascular risk, and increased clotting susceptibility. Platelets have fundamental roles in the development and propagation of inflammation and cardiovascular risk. They signal through membrane receptors, resulting in (hyper)activation and release of inflammatory molecules from platelet compartments. This review highlights how circulating inflammatory molecules, acting as platelet receptor ligands, in...
Source: Trends in Endocrinology and Metabolism: TEM - June 10, 2019 Category: Endocrinology Authors: Pretorius E Tags: Trends Endocrinol Metab Source Type: research

Anti-M üllerian Hormone in PCOS: A Review Informing International Guidelines.
Anti-Müllerian Hormone in PCOS: A Review Informing International Guidelines. Trends Endocrinol Metab. 2019 May 31;: Authors: Teede H, Misso M, Tassone EC, Dewailly D, Ng EH, Azziz R, Norman RJ, Andersen M, Franks S, Hoeger K, Hutchison S, Oberfield S, Shah D, Hohmann F, Ottey S, Dabadghao P, Laven JSE Abstract Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given recognized challenges, serum anti-Müllerian hormone (AMH) is proposed as an alternative. To inform international PCOS guideli...
Source: Trends in Endocrinology and Metabolism: TEM - May 31, 2019 Category: Endocrinology Authors: Teede H, Misso M, Tassone EC, Dewailly D, Ng EH, Azziz R, Norman RJ, Andersen M, Franks S, Hoeger K, Hutchison S, Oberfield S, Shah D, Hohmann F, Ottey S, Dabadghao P, Laven JSE Tags: Trends Endocrinol Metab Source Type: research

Circadian Clocks and Cancer: Timekeeping Governs Cellular Metabolism.
Abstract The circadian clock is a biological mechanism that dictates an array of rhythmic physiological processes. Virtually all cells contain a functional clock whose disruption results in altered timekeeping and detrimental systemic effects, including cancer. Recent advances have connected genetic disruption of the clock with multiple transcriptional and signaling networks controlling tumor initiation and progression. An additional feature of this circadian control relies on cellular metabolism, both within the tumor microenvironment and the organism systemically. A discussion of major advances related to cancer...
Source: Trends in Endocrinology and Metabolism: TEM - May 30, 2019 Category: Endocrinology Authors: Verlande A, Masri S Tags: Trends Endocrinol Metab Source Type: research