-
Imaging Biomarkers of NAFLD, NASH, and Fibrosis Mol. Metab. (IF 6.448) Pub Date : 2021-01-15 Veeral Ajmera; Rohit Loomba
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic entity that requires a liver biopsy assessment to diagnose the progressive form of NAFLD termed as nonalcoholic steatohepatitis (NASH). Liver biopsy is invasive, subject to sampling and inter-observer variability and impractical to scale to the affected population of up to 1 billion affected individuals worldwide. Non-invasive imaging
-
The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic β-cells Mol. Metab. (IF 6.448) Pub Date : 2020-12-23 Ilka Wilhelmi; Stephan Grunwald; Niclas Gimber; Oliver Popp; Gunnar Dittmar; Anup Arumughan; Erich E. Wanker; Thomas Laeger; Jan Schmoranzer; Oliver Daumke; Annette Schürmann
Objective Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood. In this work, we studied the role of the GTPase ARFRP1 on insulin secretion
-
GLP-1 and hunger modulate incentive motivation depending on insulin sensitivity in humans Mol. Metab. (IF 6.448) Pub Date : 2021-01-14 Ruth Hanssen; Alina Chloé Kretschmer; Lionel Rigoux; Kerstin Albus; Sharmili Edwin Thanarajah; Tamara Sitnikow; Corina Melzer; Oliver A. Cornely; Jens C. Brüning; Marc Tittgemeyer
Objective To regulate food intake, our brain constantly integrates external cues, such as the incentive value of a potential food reward, with internal state signals, such as hunger feelings. Incentive motivation refers to the processes that translate expected reward into effort spending to obtain the reward; the magnitude and probability of a reward involved in prompting motivated behaviour are encoded
-
Nicotinamide N-methyltransferase: at the crossroads between cellular metabolism and epigenetic regulation Mol. Metab. (IF 6.448) Pub Date : 2021-01-14 Annalisa Roberti; Agustín F. Fernández; Mario F. Fraga
Background The abundance of energy metabolites is intimately interconnected with the activity of chromatin modifying enzymes in order to guarantee the finely tuned modulation of gene expression in response to cellular energetic status. Metabolism-induced epigenetic gene regulation is a key molecular axis for the maintenance of cellular homeostasis and its deregulation is associated with several pathological
-
Essential roles of insulin and IGF-1 receptors during embryonic lineage development Mol. Metab. (IF 6.448) Pub Date : 2021-01-14 Erin R. Okawa; Manoj K. Gupta; Sevim Kahraman; Praneeth Goli; Masaji Sakaguchi; Jiang Hu; Kaiti Duan; Brittany Slipp; Jochen K. Lennerz; Rohit N. Kulkarni
The insulin and insulin-like growth factor-1 (IGF-1) receptors are important for the growth and development of embryonic tissues. To directly define their roles in the maintenance of pluripotency and differentiation of stem cells, we knocked out both the receptors in induced pluripotent stem cells (iPSCs). iPSCs lacking both the insulin and IGF-1 receptors (double knock-out, DKO) exhibited preserved
-
Insulin resistance is mechanistically linked to hepatic mitochondrial remodeling in non-alcoholic fatty liver disease Mol. Metab. (IF 6.448) Pub Date : 2020-12-23 Chris E. Shannon; Mukundan Ragavan; Juan Pablo Palavicini; Marcel Fourcaudot; Terry M Bakewell; Ivan A. Valdez; Iriscilla Ayala; Eunsook S. Jin; Muniswamy Madesh; Xianlin Han; Matthew E. Merritt; Luke Norton
Objective Insulin resistance and altered hepatic mitochondrial function are central features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), but the etiological role of these processes in disease progression remains unclear. Here we investigated the molecular links between insulin resistance, mitochondrial remodeling, and hepatic lipid accumulation. Methods Hepatic insulin sensitivity
-
Ceramides are necessary and sufficient for diet-induced impairment of thermogenic adipocytes Mol. Metab. (IF 6.448) Pub Date : 2020-12-19 Bhagirath Chaurasia; Li Ying; Chad Lamar Talbot; John Alan Maschek; James Cox; Edward H. Schuchman; Yoshio Hirabayashi; William L. Holland; Scott A. Summers
Objective Aging and weight gain lead to a decline in brown and beige adipocyte functionality that exacerbates obesity and insulin resistance. We sought to determine whether sphingolipids, such as ceramides, a class of lipid metabolites that accumulate in aging and overnutrition, are sufficient or necessary for the metabolic impairment of these thermogenic adipocytes. Methods We generated new mouse
-
Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7,8-dihydroxyflavone in female mice Mol. Metab. (IF 6.448) Pub Date : 2020-12-19 Zhenlei Zhao; Fan Xue; Yanpei Gu; Jianxin Han; Yingxian Jia; Keqiang Ye; Ying Zhang
-
Metabolic remodeling of dystrophic skeletal muscle reveals biological roles for dystrophin and utrophin in adaptation and plasticity Mol. Metab. (IF 6.448) Pub Date : 2020-12-24 Justin P. Hardee; Karen J.B. Martins; Paula M. Miotto; James G. Ryall; Stefan M. Gehrig; Boris Reljic; Timur Naim; Jin D. Chung; Jen Trieu; Kristy Swiderski; Ashleigh M. Philp; Andrew Philp; Matthew J. Watt; David A. Stroud; Rene Koopman; Gregory R. Steinberg; Gordon S. Lynch
-
Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis Mol. Metab. (IF 6.448) Pub Date : 2021-01-07 Francisco Javier Ruiz-Ojeda; Jiefu Wang; Theresa Bäcker; Martin Krueger; Samira Zamani; Simon Rosowski; Tim Gruber; Yasuhiro Onogi; Annette Feuchtinger; Tim J. Schulz; Reinhard Fässler; Timo D. Müller; Cristina García-Cáceres; Matthias Meier; Matthias Blüher; Siegfried Ussar
Objective Reorganization of the extracellular matrix is a prerequisite for healthy adipose tissue expansion, whereas fibrosis is a key feature of adipose dysfunction and inflammation. However, very little is known about the direct effects of impaired cell–matrix interaction in adipocyte function and insulin sensitivity. The objective of this study was to determine whether integrin activity can regulate
-
Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha Mol. Metab. (IF 6.448) Pub Date : 2020-12-10 Jeeyoung Lee; Mary F. Walter; Kenneth S. Korach; Constance Tom Noguchi
-
Neonatal overfeeding during lactation rapidly and permanently misaligns the hepatic circadian rhythm and programmes adult NAFLD Mol. Metab. (IF 6.448) Pub Date : 2021-01-07 Francesc Ribas-Aulinas; Silvia Ribo; Marcela Parra-Vargas; Antonio Fernández-Pérez; Judith Cebrià; Maria Guardiola-Perello; Marta Ramon-Krauel; Carles Lerin; Ruben Diaz; Susana G. Kalko; Mario Vallejo; Antoni Díez-Noguera; Trinitat Cambras; Josep C. Jimenez-Chillaron
Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver
-
Epidermal Acyl-CoA-binding protein is indispensable for systemic energy homeostasis Mol. Metab. (IF 6.448) Pub Date : 2020-12-18 Ditte Neess; Vibeke Kruse; Ann-Britt Marcher; Mie Rye Wæde; Julie Vistisen; Pauline M. Møller; Rikke Petersen; Jonathan R. Brewer; Tao Ma; Georgia Colleluori; Ilenia Severi; Saverio Cinti; Zach Gerhart-Hines; Susanne Mandrup; Nils J. Færgeman
Objectives The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously found that loss of acyl-CoA-binding protein (ACBP) in keratinocytes upregulates
-
Function of the endolysosomal network in cholesterol homeostasis and metabolic-associated fatty liver disease (MAFLD) Mol. Metab. (IF 6.448) Pub Date : 2021-01-05 Dyonne Y. Vos; Bart van de Sluis
Background Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease, has become the leading cause of chronic liver disease worldwide. In addition to hepatic accumulation of triglycerides, dysregulated cholesterol metabolism is an important contributor to the pathogenesis of MAFLD. Maintenance of cholesterol homeostasis is highly dependent on cellular cholesterol
-
Sensory neurons expressing Calcitonin Gene-Related Peptide α regulate adaptive thermogenesis and diet-induced obesity Mol. Metab. (IF 6.448) Pub Date : 2021-01-05 Kuldeep Makwana; Harshita Chodavarapu; Nancy Morones; Jingyi Chi; William Barr; Edward Novinbakht; Yidan Wang; Peter Tuan Nguyen; Predrag Jovanovic; Paul Cohen; Celine E. Riera
Objectives Heat-sensory neurons arising from the dorsal root ganglia (DRG) play a pivotal role in the detection of cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis has remained elusive. Additionally, it remains unknown whether these neurons play a
-
Hepatocyte-specific PKCβ deficiency protects against high-fat diet-induced nonalcoholic hepatic steatosis Mol. Metab. (IF 6.448) Pub Date : 2020-11-30 Yaoling Shu; Faizule Hassan; Vincenzo Coppola; Kedryn K. Baskin; Xianlin Han; Neil K. Mehta; Michael C. Ostrowski; Kamal D. Mehta
Objective Nonalcoholic hepatic steatosis, also known as fatty liver, is a uniform response of the liver to hyperlipidic-hypercaloric diet intake. However, the post-ingestive signals and mechanistic processes driving hepatic steatosis are not well understood. Emerging data demonstrate that protein kinase C beta (PKCβ), a lipid-sensitive kinase, plays a critical role in energy metabolism and adaptation
-
Nox4 mediates skeletal muscle metabolic responses to exercise Mol. Metab. (IF 6.448) Pub Date : 2021-01-02 Kalyn S. Specht; Shashi Kant; Adele K. Addington; Ryan McMillan; Matthew W. Hulver; Heather Learnard; Maura Campbell; Sarah Donnelly; Amada D. Caliz; Yongmei Pei; Michaella Reif; Jacob Bond; Anthony DeMarco; Branch Craige; John F. Keaney; Siobhan M. Craige
Objective The immediate signals that couple exercise to metabolic adaptation are incompletely understood. Nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is a producer of reactive oxygen species (ROS) and plays a significant role in both metabolic and vascular adaptation during conditions of stress. Our objective was to determine the role of Nox4 in exercise-induced skeletal muscle metabolism
-
Hepatokines and metabolism: Deciphering communication from the liver Mol. Metab. (IF 6.448) Pub Date : 2020-12-04 Sharon O. Jensen-Cody; Matthew J. Potthoff
Background The liver is a key regulator of systemic energy homeostasis and can sense and respond to nutrient excess and deficiency through crosstalk with multiple tissues. Regulation of systemic energy homeostasis by the liver is mediated in part through regulation of glucose and lipid metabolism. Dysregulation of either process may result in metabolic dysfunction and contribute to the development
-
Type 2 diabetes subgroups and potential medication strategies in relation to effects on insulin resistance and beta-cell function: a step towards personalized diabetes treatment? Mol. Metab. (IF 6.448) Pub Date : 2020-12-30 Anna Veelen; Edmundo Erazo Tapia; Jan Oscarsson; Patrick Schrauwen
Background Type 2 diabetes is a syndrome defined by hyperglycaemia that is the result of various degrees of pancreatic β-cell failure and reduced insulin sensitivity. Despite the fact that diabetes can be caused by multiple metabolic dysfunctions, the majority of patients are defined as having either type 1 or type 2 diabetes. Recently, Ahlqvist and colleagues proposed a new way to classify patients
-
White adipose remodeling during browning in mice involves YBX1 to drive thermogenic commitment Mol. Metab. (IF 6.448) Pub Date : 2020-12-05 Atefeh Rabiee; Kaja Plucińska; Marie Sophie Isidor; Erin Louise Brown; Marco Tozzi; Simone Sidoli; Patricia Stephanie S. Petersen; Marina Agueda-Oyarzabal; Silje Bøen Torsetnes; Galal Nazih Chehabi; Morten Lundh; Ali Altıntaş; Romain Barrès; Ole Nørregaard Jensen; Zachary Gerhart-Hines; Brice Emanuelli
-
Adaptive thermogenesis in brown adipose tissue involves activation of pannexin-1 channels Mol. Metab. (IF 6.448) Pub Date : 2020-11-25 Subramanian Senthivinayagam; Vlad Serbulea; Clint M. Upchurch; Renata Polanowska-Grabowska; Suresh K. Mendu; Srabani Sahu; Prathiba Jayaguru; Kevin W. Aylor; Mahendra D. Chordia; Limor Steinberg; Nathaniel Oberholtzer; Seichii Uchiyama; Noriko Inada; Ulrike M. Lorenz; Thurl E. Harris; Susanna R. Keller; Akshaya K. Meher; Alexandra Kadl; Norbert Leitinger
Objective Brown adipose tissue (BAT) is specialized in thermogenesis. The conversion of energy into heat in brown adipocytes proceeds via stimulation of β-adrenergic receptor (βAR)-dependent signaling and activation of mitochondrial uncoupling protein 1 (UCP1). We have previously demonstrated a functional role for pannexin-1 (Panx1) channels in white adipose tissue; however, it is not known whether
-
FGF19 and FGF21. In NASH We Trust Mol. Metab. (IF 6.448) Pub Date : 2020-12-29 Saswata Talukdar; Alexei Kharitonenkov
Fibroblast Growth Factors 19 and 21 (FGF19 and FGF21) are novel endocrine messengers that regulate multiple aspects of energy homeostasis. The magnitude and pleotropic character of their beneficial actions on many, if not all abnormalities of the metabolic syndrome in animals led to extensive exploration of their biology and coordinated efforts to design novel FGF19/21-based analogs for therapeutic
-
Centrally circulating α-klotho inversely correlates with human obesity and modulates arcuate cell populations in mice Mol. Metab. (IF 6.448) Pub Date : 2020-12-07 Taylor Landry; Peixin Li; Daniel Shookster; Zhiying Jiang; Hongli Li; Brenton Thomas Laing; Wyatt Bunner; Theodore Langton; Qingchun Tong; Hu Huang
-
Pancreatic, but not myeloid-cell, expression of interleukin-1alpha is required for maintenance of insulin secretion and whole body glucose homeostasis Mol. Metab. (IF 6.448) Pub Date : 2020-12-05 J. Jason Collier; Heidi M. Batdorf; Thomas M. Martin; Kristen E. Rohli; David H. Burk; Danhong Lu; Chris R. Cooley; Michael D. Karlstad; Joseph W. Jackson; Tim E. Sparer; Jingying Zhang; Randall L. Mynatt; Susan J. Burke
Objective The expression of the interleukin-1 receptor type I (IL-1R) is enriched in pancreatic islet β-cells, signifying that ligands activating this pathway are important for the health and function of the insulin-secreting cell. Using isolated mouse, rat, and human islets, we identified the cytokine IL-1α as a highly inducible gene in response to IL-1R activation. In addition, IL-1α is elevated
-
Testosterone metabolites differentially regulate obesogenesis and fat distribution Mol. Metab. (IF 6.448) Pub Date : 2020-12-09 Zachary L. Sebo; Matthew S. Rodeheffer
Objective Low testosterone in men (hypogonadism) is associated with obesity and type II diabetes. Testosterone replacement therapy has been shown to reverse these effects. However, the mechanisms by which testosterone regulates total fat mass, fat distribution, and metabolic health are unclear. In this study, we clarify the impact of hypogonadism on these parameters, as well as parse the role of testosterone
-
Amylin receptor insensitivity impairs hypothalamic POMC neuron differentiation in the male offspring of maternal high-fat diet-fed mice Mol. Metab. (IF 6.448) Pub Date : 2020-12-03 Cheng Li; Jing-Jing Xu; Hong-Tao Hu; Chao-Yi Shi; Chuan-Jin Yu; Jian-Zhong Sheng; Yan-Ting Wu; He-Feng Huang
-
Hepatic synthesis of triacylglycerols containing medium-chain fatty acids is dominated by diacylglycerol acyltransferase 1 and efficiently inhibited by etomoxir Mol. Metab. (IF 6.448) Pub Date : 2020-12-23 Klaus Wunderling; Christina Leopold; Isabell Jamitzky; Mohamed Yaghmour; Fabian Zink; Dagmar Kratky; Christoph Thiele
-
Nuclear Hormone and Peptide Hormone Therapeutics for NAFLD and NASH Mol. Metab. (IF 6.448) Pub Date : 2020-12-23 Brian Finan; Sebastian D. Parlee; Bin Yang
Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic
-
Characterization of viral insulins reveals white adipose tissue-specific effects in mice Mol. Metab. (IF 6.448) Pub Date : 2020-11-19 Martina Chrudinová; François Moreau; Hye Lim Noh; Terezie Páníková; Lenka Žáková; Randall H. Friedline; Francisco A. Valenzuela; Jason K. Kim; Jiří Jiráček; C. Ronald Kahn; Emrah Altindis
Objective Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously
-
Intestinal stem cell-derived enteroids from morbidly obese patients preserve obesity-related phenotypes: Elevated glucose absorption and gluconeogenesis Mol. Metab. (IF 6.448) Pub Date : 2020-11-25 Nesrin M. Hasan; Kelli F. Johnson; Jianyi Yin; Nicholas W. Baetz; Lea Fayad; Vadim Sherman; Sarah E. Blutt; Mary K. Estes; Vivek Kumbhari; Nicholas C. Zachos; Olga Kovbasnjuk
Objective The mechanisms behind the efficacy of bariatric surgery (BS) for treating obesity and type 2 diabetes, particularly with respect to the influence of the small bowel, remain poorly understood. In vitro and animal models are suboptimal with respect to their ability to replicate the human intestinal epithelium under conditions induced by obesity. Human enteroids have the potential to accelerate
-
LKB1 deficiency-induced metabolic reprogramming in tumorigenesis and non-neoplastic diseases Mol. Metab. (IF 6.448) Pub Date : 2020-12-03 Yanghe Zhang; Qingfei Meng; Qianhui Sun; Zhi-Xiang Xu; Honglan Zhou; Yishu Wang
Background Live kinase B1 (LKB1) is a tumor suppressor that is mutated in Peutz-Jeghers syndrome (PJS) and a variety of cancers. Lkb1 encodes serine-threonine kinase (STK) 11 that activates AMP-activated protein kinase (AMPK) and its 13 superfamily members, regulating multiple biological processes, such as cell polarity, cell cycle arrest, embryo development, apoptosis, and bioenergetics metabolism
-
Small intestinal taurochenodeoxycholic acid-FXR axis alters local nutrient-sensing glucoregulatory pathways in rats Mol. Metab. (IF 6.448) Pub Date : 2020-11-29 T.M. Zaved Waise; Yu-Mi Lim; Zahra Danaei; Song-Yang Zhang; Tony K.T. Lam
Objective The mechanism of nutrient sensing in the upper small intestine (USI) and ileum that regulates glucose homeostasis remains elusive. Short-term high-fat (HF) feeding increases taurochenodeoxycholic acid (TCDCA; an agonist of farnesoid X receptor (FXR)) in the USI and ileum of rats, and the increase of TCDCA is prevented by transplantation of microbiota obtained from the USI of healthy donors
-
Metabolic drivers of non-alcoholic fatty liver disease Mol. Metab. (IF 6.448) Pub Date : 2020-12-17 Kendra K. Bence; Morris J. Birnbaum
Background The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing rapidly worldwide in parallel to the global obesity epidemic. NAFLD encompasses a range of liver pathologies and most often originates from metabolically driven accumulation of fat in the liver, or nonalcoholic fatty liver (NAFL). In a subset of people with NAFL, the disease can progress to nonalcoholic steatohepatitis
-
Targeting the GIPR for Obesity: To Agonize or Antagonize? Potential Mechanisms Mol. Metab. (IF 6.448) Pub Date : 2020-12-05 Jonathan E. Campbell
Background Glucose-dependent insulinotropic peptide (GIP) is one of two incretin hormones that communicate nutrient intake with systemic metabolism. Although GIP was the first incretin hormone to be discovered, the understanding of GIP biology was quickly outpaced by the research focusing on the other incretin hormone, glucagon-like peptide 1 (GLP-1). Early work on GIP produced the notion that GIP
-
Mitochondrial oxidative function in NAFLD: friend or foe? Mol. Metab. (IF 6.448) Pub Date : 2020-12-01 Michael Shum; Jennifer Ngo; Orian S. Shirihai; Marc Liesa
Background Mitochondrial oxidative function plays a key role in the development of non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR). Recent studies support that fatty liver might not be a result of decreased mitochondrial fat oxidation caused by mitochondrial damage. Rather, NAFLD and IR cause an elevation in mitochondrial function, which covers the increased demand for carbon
-
“A LEAP 2 Conclusions?: Targeting the Ghrelin System to Treat Obesity and Diabetes” Mol. Metab. (IF 6.448) Pub Date : 2020-11-25 Deepali Gupta; Sean B. Ogden; Kripa Shankar; Salil Varshney; Jeffrey M. Zigman
Background The hormone ghrelin stimulates food intake, promotes adiposity, increases body weight, and elevates blood glucose. Consquently, alterations in plasma ghrelin levels and the functioning of other components of the broader ghrelin system have been proposed as potential contributors to obesity and diabetes. Furthermore, targeting the ghrelin system has been proposed as a novel therapeutic strategy
-
A multi-component screen for feeding behaviour and nutritional status in Drosophila to interrogate mammalian appetite-related genes Mol. Metab. (IF 6.448) Pub Date : 2020-11-23 J. Chalmers; Y.C.L. Tung; C.H. Liu; C.J. O'Kane; S. O'Rahilly; G.S.H. Yeo
Objective More than 300 genetic variants have been robustly associated with measures of human adiposity. Highly penetrant mutations causing human obesity do so largely by disrupting satiety pathways in the brain and increasing food intake. Most of the common obesity-predisposing variants are in, or near, genes that are expressed highly in the brain, but little is known about their function. Exploring
-
Inhibition of Mitochondrial Fission and iNOS in the Dorsal Vagal Complex Protects from Overeating and Weight Gain Mol. Metab. (IF 6.448) Pub Date : 2020-11-20 Bianca Patel; Lauryn E. New; Joanne C. Griffiths; Jim Deuchars; Beatrice M. Filippi
The dorsal vagal complex (DVC) senses insulin and controls glucose homeostasis, feeding behaviour and bodyweight. Three-days of high-fat diet (HFD) in rats are sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased dynamin-related protein 1 (Drp1)-dependent mitochondrial fission in the DVC. Higher Drp1 activity
-
Non-alcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans Mol. Metab. (IF 6.448) Pub Date : 2020-11-19 Kalliopi Pafili; Michael Roden
Background Non-alcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (non-alcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly arising from the worldwide obesity and diabetes epidemics. Scope of review This
-
Behavioural and neurochemical mechanisms underpinning the feeding-suppressive effect of GLP-1/CCK combinatorial therapy Mol. Metab. (IF 6.448) Pub Date : 2020-11-19 Emma Roth; Simon Benoit; Baptiste Quentin; Brian Lam; Sarah Will; Marcella Ma; Nick Heeley; Tamana Darwish; Yashaswi Shrestha; Fiona Gribble; Frank Reimann; Irina Pshenichnaya; Giles Yeo; David J. Baker; James L. Trevaskis; Clemence Blouet
Combinatorial therapies are under intense investigation for the development of more efficient anti-obesity drugs, however little is known about how they act in brain to produce enhanced anorexia and weight loss. Objectives The goal of this study was to identify the brain sites and neuronal populations engaged during the co-administration of GLP-1R and CCK1R agonists, an efficient combination therapy
-
Female mice exposed to low doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes Mol. Metab. (IF 6.448) Pub Date : 2020-10-16 Myriam P. Hoyeck; Rayanna C. Merhi; Hannah L. Blair; C. Duncan Spencer; Mikayla A. Payant; Diana I. Martin Alfonso; Melody Zhang; Geronimo Matteo; Melissa J. Chee; Jennifer E. Bruin
Objective Exposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of transient low-dose dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life
-
Autocrine negative feedback regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT Mol. Metab. (IF 6.448) Pub Date : 2020-10-19 Anna Sofie Husted; Jeppe H. Ekberg; Emma Tripp; Tinne A.D. Nissen; Stijn Meijnikman; Shannon L. O'Brien; Trond Ulven; Yair Acherman; Sjoerd C. Bruin; Max Nieuwdorp; Zach Gerhart-Hines; Davide Calebiro; Lars O. Dragsted; Thue W. Schwartz
-
Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease Mol. Metab. (IF 6.448) Pub Date : 2020-11-18 Yang Xiao; Mindy Kim; Mitchell A. Lazar
Background As a result of a sedentary lifestyle and excess food consumption in modern society, non-alcoholic fatty liver disease (NAFLD) characterized by fat accumulation in the liver is becoming a major disease burden. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, characterized by inflammation and fibrosis which can lead to hepatocellular carcinoma and liver failure. Nuclear receptors
-
Beige fat is dispensable for the metabolic benefits associated with myostatin deletion Mol. Metab. (IF 6.448) Pub Date : 2020-11-18 François Marchildon; Jingyi Chi; Sean O’Connor; Hilary Bediako; Paul Cohen
Objective Increasing muscle mass and activating beige fat both have great potential for ameliorating obesity and its comorbidities. Myostatin null mice have increased skeletal muscle mass and are protected from obesity and its sequelae. Deletion of myostatin has also been suggested to result in the activation of beige adipocytes, thermogenic fat cells with anti-obesity and anti-diabetes properties
-
Growth differentiation factor 15 as a potential therapeutic for the treatment of obesity Mol. Metab. (IF 6.448) Pub Date : 2020-11-18 Clarence Hale; Murielle M. Véniant
Background Obesity is rapidly becoming one of the world’s most critical health care concerns. Comorbidities accompanying excess weight include cardiovascular disease, diabetes, and certain cancers. These comorbidities result in greater hospitalization and other health care-related costs. Economic impacts are likely to be felt more acutely in developing countries, where obesity rates continue to rise
-
Maternal obesity persistently alters cardiac progenitor gene expression and programs adult-onset heart disease susceptibility Mol. Metab. (IF 6.448) Pub Date : 2020-11-17 Abdalla Ahmed; Minggao Liang; Lijun Chi; Yu-Qing Zhou; John G. Sled; Michael D. Wilson; Paul Delgado-Olguín
-
Loss of protein kinase D activity demonstrates redundancy in cardiac glucose metabolism and preserves cardiac function in obesity Mol. Metab. (IF 6.448) Pub Date : 2020-10-21 Kirstie A. De Jong; Liam G. Hall; Mark C. Renton; Timothy Connor; Sheree D. Martin; Greg M. Kowalski; Christopher S. Shaw; Clinton R. Bruce; Kirsten F. Howlett; Sean L. McGee
Objective Protein kinase D (PKD) signaling has been implicated in stress-induced cardiac remodeling and function as well as metabolic processes including contraction-mediated cardiac glucose uptake. PKD has recently emerged as a nutrient-sensing kinase that is activated in high-lipid environments, such as in obesity. However, the role of PKD signaling in cardiac glucose metabolism and cardiac function
-
Hepatic lipid droplets: a balancing act between energy storage and metabolic dysfunction in NAFLD Mol. Metab. (IF 6.448) Pub Date : 2020-11-10 Douglas G. Mashek
Background Non-alcoholic fatty liver disease (NAFLD) is defined by the abundance of lipid droplets (LDs) in hepatocytes. While historically considered simply a depot for energy storage, LDs are increasingly recognized to impact a wide range of biological processes that influence cellular metabolism, signaling, and function. While progress has been made towards our understanding of factors leading to
-
FGF15/19 is required for adipose tissue plasticity in response to thermogenic adaptation Mol. Metab. (IF 6.448) Pub Date : 2020-11-07 Samantha Morón-Ros; Iker Uriarte; Carmen Berasain; Matías A. Avila; Mònica Sabater-Masdeu; José María Moreno-Navarrete; José Manuel Fernández-Real; Marta Giralt; Francesc Villarroya; Aleix Gavaldà-Navarro
Objective To determine the role of the enterokine, FGF15/19, in adipose tissue thermogenic adaptations. Methods Circulating FGF19 and gene expression (qRT-PCR) levels were assessed in subcutaneous adipose tissue from human patients with obesity. Effects of experimentally increased FGF15 and FGF19 levels in vivo were determined in mice using adenoviral and adeno-associated vectors. Adipose tissues were
-
Mono- and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases Mol. Metab. (IF 6.448) Pub Date : 2020-11-07 Nina Sonne; Morten A. Karsdal; Kim Henriksen
Background Therapies for metabolic diseases are numerous, yet improvement of insulin sensitivity beyond that induced by weight loss has remained elusive. Therefore, there is a continued search for novel treatment candidates that can stimulate insulin sensitivity and increase the efficacy on weight loss in combination with current treatment options. Calcitonin gene-related peptide (CGRP) and amylin
-
Interaction between magnesium and methylglyoxal in diabetic polyneuropathy and neuronal models Mol. Metab. (IF 6.448) Pub Date : 2020-11-06 Alexander Strom; Klaus Strassburger; Martin Schmuck; Hanna Shevalye; Eric Davidson; Fariba Zivehe; Gidon Bönhof; Rudolph Reimer; Bengt-Frederik Belgardt; Thomas Fleming; Barbara Biermann; Volker Burkart; Karsten Müssig; Julia Szendroedi; Mark A. Yorek; Ellen Fritsche; Peter P. Nawroth; Michael Roden; Dan Ziegler
Objective The lack of effective treatments against diabetic sensorimotor polyneuropathy demands the search for new strategies to combat or prevent the condition. Since reduced magnesium and increased methylglyoxal levels have been implicated in the development of both type 2 diabetes and neuropathic pain, we aimed to assess the putative interplay of both molecules with diabetic sensorimotor polyneuropathy
-
Genetic and epigenetic factors determining NAFLD risk Mol. Metab. (IF 6.448) Pub Date : 2020-11-05 Wenke Jonas; Annette Schürmann
Hepatic steatosis is a common chronic liver disease that can progress into more severe stages of NAFLD or promote the development of life-threatening secondary diseases for a part of the affected people. These include the liver itself (nonalcoholic steatohepatitis or NASH; fibrosis and cirrhosis, and hepatocellular carcinoma) or other organs such as the vessels and the heart (cardiovascular disease)
-
Insulin and obesity transforms hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state Mol. Metab. (IF 6.448) Pub Date : 2020-11-04 Martin Werdermann; Ilona Berger; Laura D. Scriba; Alice Santambrogio; Pia Schlinkert; Heike Brendel; Henning Morawietz; Andreas Schedl; Mirko Peitzsch; Aileen J.F. King; Cynthia L. Andoniadou; Stefan R. Bornstein; Charlotte Steenblock
Objective Metabolic diseases are an increasing problem in our society with the brain-metabolic axis as a master regulator of the human body for sustaining homeostasis under metabolic stress. On the other hand, metabolic inflammation and disease will trigger a sustained activation of the hypothalamic-pituitary-adrenal axis. In this study, we investigated the role of metabolic stress on progenitor cells
-
Review: Glucose-sensitive insulin Mol. Metab. (IF 6.448) Pub Date : 2020-10-31 Thomas Hoeg-Jensen
Background Hypoglycaemia, the frightening condition of low blood sugar, is a common occurrence in people with diabetes using insulin therapy. The idea of protecting against hypoglycaemia by engineering an insulin preparation that can auto-adjust its biological activity to fluctuating blood glucose levels has been pursued since the 1970’s, but despite thousands of publications, no system that works
-
Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms Mol. Metab. (IF 6.448) Pub Date : 2020-10-31 Nicholas J. Saner; Matthew J-C Lee; Jujiao Kuang; Nathan W. Pitchford; Gregory D. Roach; Andrew Garnham; Amanda J. Genders; Tanner Stokes; Elizabeth A. Schroder; Zhiguang Huo; Karyn A. Esser; Stuart M. Phillips; David J. Bishop; Jonathan D. Bartlett
Objective Sleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Given that exercise improves glucose tolerance, mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects
-
The absence of hepatic glucose-6 phosphatase/ChREBP couple is incompatible with survival in mice Mol. Metab. (IF 6.448) Pub Date : 2020-10-31 Fabienne Rajas; Renaud Dentin; Alexane Cannella; Marine Silva; Margaux Raffin; Françoise Levavasseur; Amandine Gautier-Stein; Catherine Postic; Gilles Mithieux
Objective Glucose production into the blood requires the expression of glucose-6 phosphatase (G6Pase), a key enzyme that allows glucose-6 phosphate (G6P) hydrolysis into free glucose and inorganic phosphate. We previously reported that the hepatic suppression of G6Pase leads to G6P accumulation and to metabolic reprogramming in hepatocytes from liver G6Pase deficient mice (L.G6pc-/-). Interestingly
-
Moderate SIRT1 overexpression protects against brown adipose tissue inflammation Mol. Metab. (IF 6.448) Pub Date : 2020-10-10 Carmen Escalona-Garrido; Patricia Vázquez; Paula Mera; Sebastián Zagmutt; Ester García-Casarrubios; Ana Montero-Pedrazuela; Fernanda Rey-Stolle; Ana Guadaño-Ferraz; Francisco J. Rupérez; Dolors Serra; Laura Herrero; Maria Jesus Obregon; Ángela M. Valverde
-
The role of exercise-induced peripheral factors in sleep regulation Mol. Metab. (IF 6.448) Pub Date : 2020-10-09 Xiao Tan; Lieve T. van Egmond; Jonathan Cedernaes; Christian Benedict
Background Recurrently disrupted sleep is a widespread phenomenon in our society. This is worrisome as chronically impaired sleep increases the risk of numerous diseases that place a heavy burden on health services worldwide, including type 2 diabetes, obesity, depression, cardiovascular disease, and dementia. Therefore, strategies mitigating the current societal sleep crisis are needed. Scope of review
-
Dysregulated lipid metabolism links NAFLD to cardiovascular disease Mol. Metab. (IF 6.448) Pub Date : 2020-10-01 Audrey Deprince; Joel T. Haas; Bart Staels
Background Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a global health problem. Cardiovascular diseases (CVD) are the most common cause of mortality in NAFLD patients. NAFLD and CVD share several common risk factors including obesity, insulin resistance, and type 2 diabetes (T2D). Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense low-density
-
Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment Mol. Metab. (IF 6.448) Pub Date : 2020-09-30 Yuki Maeda; Ryota Kikuchi; Junichiro Kawagoe; Takao Tsuji; Nobuyuki Koyama; Kazuhiro Yamaguchi; Hiroyuki Nakamura; Kazutetsu Aoshiba