Obesity

  • Article
    | Open Access

    Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.

    • Xin Cui
    • , Jia Jing
    •  & Hang Shi
  • Article
    | Open Access

    Tissue circadian clocks contribute to the regulation of physiology and metabolism. Here the authors investigate the role of the intestinal circadian clock in energy homeostasis and show that the intestinal clock acts as an accelerator in dietary fat absorption.

    • Fangjun Yu
    • , Zhigang Wang
    •  & Baojian Wu
  • Article
    | Open Access

    Many genetic loci have been linked to obesity, but knowledge of their functional mechanisms is limited. Here, the authors perform reporter assays and temporal functional genomics data generation to characterize obesity genetic loci and find that loci often harbor multiple functional variants.

    • Amelia C. Joslin
    • , Débora R. Sobreira
    •  & Marcelo A. Nóbrega
  • Article
    | Open Access

    The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here the authors report that inactivation of the orexin receptor type 1 or 2 in serotonergic neurons differentially regulate systemic glucose homeostasis in the context of diet induced obesity.

    • Xing Xiao
    • , Gagik Yeghiazaryan
    •  & A. Christine Hausen
  • Article
    | Open Access

    Calcitonin receptor-expressing neurons of the nucleus tractus solitarius contribute to long-term control of food intake and body weight. The authors show that a subset of these cells expresses Prlh and that enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity in mice.

    • Wenwen Cheng
    • , Ermelinda Ndoka
    •  & Martin G. Myers Jr
  • Article
    | Open Access

    Hyaluronan is a naturally occurring linear polysaccharide that together with collagens, enzymes, and glycoproteins forms the extracellular matrix. Here the authors show that adipose tissue overproduction of Hyaluronan reduces fat accumulation in mice fed high-fat diet and improves systemic glucose homeostasis.

    • Yi Zhu
    • , Na Li
    •  & Philipp E. Scherer
  • Article
    | Open Access

    The mechanisms that mediate the effects of weight loss surgeries such as vertical sleeve gastrectomy (VSG) are incompletely understood. Here the authors show that intestinal FGF15 is necessary to improve glucose tolerance and to prevent the loss of muscle and bone mass after VSG, potentially via protection against bile acid toxicity.

    • Nadejda Bozadjieva-Kramer
    • , Jae Hoon Shin
    •  & Randy J. Seeley
  • Article
    | Open Access

    Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.

    • Allison L. Fisher
    • , Veena Sangkhae
    •  & Elizabeta Nemeth
  • Article
    | Open Access

    During the expansion of adipose tissue adipocyte progenitor cells proliferate and undergo adipogenesis. Here, the authors show that adipocyte progenitor cell proliferation in visceral adipose tissue has a diurnal pattern, which is dependent on both energy intake and the circadian clock.

    • Aleix Ribas-Latre
    • , Rafael Bravo Santos
    •  & Kristin L. Eckel-Mahan
  • Article
    | Open Access

    Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.

    • Vincenza Cifarelli
    • , Sila Appak-Baskoy
    •  & Nada A. Abumrad
  • Article
    | Open Access

    Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.

    • Calvin C. Chan
    • , Isaac T. W. Harley
    •  & Senad Divanovic
  • Review Article
    | Open Access

    At the centre of intestinal health and the fight against obesity and metabolic syndrome is the intestinal microbiota and its interaction with our immune systems. Here the authors Review the current understanding of how these systems interact and how we can capitalize on recent advances to provide better therapeutic options.

    • Saad Khan
    • , Helen Luck
    •  & Daniel A. Winer
  • Article
    | Open Access

    Whether chronic inflammation contributes to metabolic disease through the dysregulation of circadian systems remains incompletely understood in humans. Here the authors show that circadian clock function is perturbed in adipose tissue from individuals with obesity, and that inhibition of NFkB improves clock function.

    • Eleonore Maury
    • , Benoit Navez
    •  & Sonia M. Brichard
  • Article
    | Open Access

    Hedonic feeding occurs in the absence of metabolic need and plays a critical role in the excessive feeding that underlies obesity. The authors show that optogenetic manipulation of NAc inputs from the prefrontal cortex versus inputs from the anterior paraventricular nucleus of the thalamus has opposite effects on high fat intake.

    • Daniel J. Christoffel
    • , Jessica J. Walsh
    •  & Robert C. Malenka
  • Article
    | Open Access

    Adipose tissue is composed of a variety of cell types, including adipocyte precursor populations, that contribute to adipose tissue function upon differentiation. Here, using scRNA-sequencing of adolescent and adult mouse subcutaneous adipose tissue, the authors identify an Asc-1 positive preadipocyte population that is enriched in adolescent subcutaneous fat and demonstrate that loss of Asc-1 triggers spontaneous beige adipocyte differentiation.

    • Lisa Suwandhi
    • , Irem Altun
    •  & Siegfried Ussar
  • Article
    | Open Access

    Blood circulating proteins reflect biological processes, thus providing insight into complex traits. Here the authors study the relationship between 1000 plasma proteins and body mass index (BMI), highlighting widespread proteome changes and causal relationships between BMI and specific proteins.

    • Shaza B. Zaghlool
    • , Sapna Sharma
    •  & Karsten Suhre
  • Article
    | Open Access

    Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model.

    • Benjamin A. H. Jensen
    • , Jacob B. Holm
    •  & Tor E. Lea
  • Review Article
    | Open Access

    The gastrointestinal tract participates in maintaining metabolic homeostasis in part through nutrient-sensing and subsequent gut-brain signalling. Here the authors review the role of small intestinal nutrient-sensing in regulation of energy intake and systemic glucose metabolism, and link high-fat diet, obesity and diabetes with perturbations in these pathways.

    • Frank A. Duca
    • , T. M. Zaved Waise
    •  & Tony K. T. Lam
  • Article
    | Open Access

    Western diet is one of the major causes underlying diabetes, and the microbes residing in the gut playing a critical role in mediating the effects of diet. Here the authors utilize network analysis to discover two species of Lactobacilli decreased by western diet, which improve glucose metabolism and restore of hepatic mitochondria in mice.

    • Richard R. Rodrigues
    • , Manoj Gurung
    •  & Natalia Shulzhenko
  • Article
    | Open Access

    The genetic determinants of sex-specific differences in obesity are still incompletely understood. Here, the authors demonstrate that adipocyte specific loss of Trim28 in committed adipocytes leads to sex specific differences in the development of obesity, and that this phenotype is associated with altered metabolic flexibility and lipid metabolism.

    • Simon T. Bond
    • , Emily J. King
    •  & Brian G. Drew
  • Article
    | Open Access

    The prevalence of cardiometabolic diseases (CMDs) is increasing rapidly across Africa. Here, the authors investigate autozygosity in CMD-associated traits in over 10,000 sub-Saharan African individuals, showing these traits are influenced by sex-specific inbreeding depression and environmental interactions.

    • Francisco C. Ceballos
    • , Scott Hazelhurst
    •  & Michèle Ramsay
  • Article
    | Open Access

    The expansion of the white adipose tissue during obesity is accompanied by increased cellular stress, but factors that protect adipocytes from cell death are not well known. Here the authors report that the transcriptional co-activators YAP and TAZ are activated in adipocytes during obesity, which increases adipocyte survival through the proapoptotic factor BIM.

    • Lei Wang
    • , ShengPeng Wang
    •  & Stefan Offermanns
  • Article
    | Open Access

    Both agonism and antagonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR) lead to weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Here the authors show that this may be explained by desensitization of GIPR activity by chronic GIPR agonism in vitro and in vivo.

    • Elizabeth A. Killion
    • , Michelle Chen
    •  & David J. Lloyd
  • Article
    | Open Access

    Defective rhythmic metabolism is associated with high-fat diet feeding and obesity. The authors show that the clock gene BMAL1 drives paraventricular hypothalamic neuron activity via rhythmic GABAergic neurotransmission, and that this mediates diurnal metabolism and diet-induced obesity.

    • Eun Ran Kim
    • , Yuanzhong Xu
    •  & Qingchun Tong
  • Article
    | Open Access

    Inflammation, immune cells and the host microbiota are intimately linked in the pathophysiology of obesity and diabetes. Here the authors show mucosal-associated invariant T cells fuel inflammation in the tissues and serve a function in promoting metabolic breakdown, polarising macrophage populations and inducing dysbiosis of the intestinal microbiota.

    • Amine Toubal
    • , Badr Kiaf
    •  & Agnès Lehuen
  • Article
    | Open Access

    Immune cells are important regulators of adipose tissue function, including adaptive thermogenesis. Here the authors show that mice with Krüppel-like factor 3 (KLF3) deficiency in bone marrow-derived cells have increased adipose tissue beiging which may at least in part be due to altered eosinophil paracrine signaling.

    • Alexander J. Knights
    • , Emily J. Vohralik
    •  & Kate G. R. Quinlan
  • Article
    | Open Access

    White adipose inflammation can occur in obesity and is at least in part mediated by inflammatory immune cells. Here the authors show that the Type I Interferon/Interferon alpha-beta receptor axis promotes an inflammatory, glycolysis associated adipocyte phenotype.

    • Calvin C. Chan
    • , Michelle S. M. A. Damen
    •  & Senad Divanovic
  • Article
    | Open Access

    Obesity and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance in skeletal muscle. Here, the authors map skeletal muscle enhancer elements dynamically regulated after exposure to free fatty acid palmitate or inflammatory cytokine TNFα and identify target genes involved in metabolic dysfunction in skeletal muscle.

    • Kristine Williams
    • , Lars R. Ingerslev
    •  & Romain Barrès
  • Article
    | Open Access

    Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

    • Katrin Fischer
    • , Anna Fenzl
    •  & Timo D. Müller
  • Article
    | Open Access

    Understanding the regulatory mechanisms governing brown and beige adipose mediated thermogenesis is of interest in order to develop therapeutic strategies to treat obesity. Here, the authors show that adipocyte-expressed apoptosis signal-regulating kinase 1 (ASK1) inhibits browning in response to cold, β3 receptor activation, and LPS.

    • Fabrizio C. Lucchini
    • , Stephan Wueest
    •  & Daniel Konrad
  • Article
    | Open Access

    Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.

    • Mohsen Fathzadeh
    • , Jiehan Li
    •  & Joshua W. Knowles
  • Article
    | Open Access

    In response to insulin, liver cells increase de novo lipogenesis via the transcription factors USF-1 and SREBP. Here the authors show that USF-1 recruits JMJD1C, after its phosphorylation by mTOR, to lipogenic promoters where JMJD1C demethylates histone H3, contributing to lipogenesis by an epigenetic mechanism.

    • Jose A. Viscarra
    • , Yuhui Wang
    •  & Hei Sook Sul
  • Article
    | Open Access

    Despite widespread transcription of LncRNA in mammalian systems, their contribution to metabolic homeostasis at the cellular and tissue level remains elusive. Here Pradas-Juni et al. describe a transcription factor–LncRNA pathway that couples hepatocyte nutrient sensing to regulation of glucose metabolism in mice.

    • Marta Pradas-Juni
    • , Nils R. Hansmeier
    •  & Jan-Wilhelm Kornfeld
  • Article
    | Open Access

    Serotonin inhibits adipose tissue thermogenesis. Here the authors show that obese mice housed in thermoneutrality have increased mast cell serotonin synthesis, and that inhibiting this pathway through deletion of mast cell Tph1 increases white adipose tissue browning and protects against diet-induced obesity, insulin resistance and liver steatosis.

    • Julian M. Yabut
    • , Eric M. Desjardins
    •  & Gregory R. Steinberg
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    •  & Benoit Chassaing
  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    •  & John M. Mariadason
  • Article
    | Open Access

    Surgical weight-loss interventions improve insulin sensitivity via incompletely understood mechanisms. Here the authors assess skeletal muscle epigenetic changes in individuals with obesity following metabolic surgery and compare them with data from individuals without obesity.

    • Sofiya Gancheva
    • , Meriem Ouni
    •  & Michael Roden
  • Article
    | Open Access

    The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.

    • Daniel Wilinski
    • , Jasmine Winzeler
    •  & Monica Dus
  • Article
    | Open Access

    While many pleiotropic genetic loci have been identified, how they contribute to phenotypes across traits and diseases is unclear. Here, the authors propose decomposition of genetic associations (DeGAs), which uses singular value decomposition, to characterize the underlying latent structure of genetic associations of 2,138 phenotypes.

    • Yosuke Tanigawa
    • , Jiehan Li
    •  & Manuel A. Rivas