Abstract：
OBJECTIVE:Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' posits that the capacity to increase the size and number of adipocytes is finite and that when this limit is exceeded, fat accumulates in ectopic sites and leads to metabolic disease. METHODS:Here we studied the energetic and biochemical consequences of short-term (2-day) excess fat ingestion in a lipodystrophic (A-ZIP/F-1) mouse model in which adipose capacity is severely restricted. RESULTS:In wildtype littermates, this acute exposure to high fat diets resulted in excess energy intake and weight gain without any significant changes in macronutrient oxidation rates, glucose, TAG, or insulin levels. In contrast, hyperphagic lipodystrophic mice failed to gain weight; rather, they significantly increased hepatic steatosis and fat oxidation. This response was associated with a significant increase in hyperglycemia, hyperinsulinemia, glucosuria, hypertriglyceridemia, and worsening insulin tolerance. CONCLUSIONS:These data suggest that when adipose storage reserves are saturated, excess fat intake necessarily increases fat oxidation and induces oxidative substrate competition which exacerbates insulin resistance resolving any residual energy surplus through excretion of glucose.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Girousse A,Virtue S,Hart D,Vidal-Puig A,Murgatroyd PR,Mouisel E,Sengenès C,Savage DBdoi
10.1016/j.molmet.2018.05.006subject
Has Abstractpub_date
2018-07-01 00:00:00pages
24-29issn
2212-8778pii
S2212-8778(18)30345-4journal_volume
13pub_type
杂志文章abstract：OBJECTIVE:Glucagon is a hormone with metabolic actions that maintains normoglycemia during the fasting state. Strategies enabling either inhibition or activation of glucagon receptor (Gcgr) signaling are being explored for the treatment of diabetes or obesity. However, the cardiovascular consequences of manipulating gl...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.11.005
更新日期：2014-11-29 00:00:00
abstract：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 ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101120
更新日期：2021-01-01 00:00:00
abstract：BACKGROUND: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 resistanc...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.101153
更新日期：2020-12-23 00:00:00
abstract：OBJECTIVE:Studies using the estrogen receptor alpha (ERα) knock-out (αERKO) mice have demonstrated that ERα plays a crucial role in various estrogen-mediated metabolic regulations. ERα is a ligand dependent transcription regulator and its activity is regulated by estrogenic compounds. ERα consists of two transcriptiona...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.09.006
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:Modern lifestyles, especially high-caloric intake and physical inactivity, contribute to the increased prevalence of non-alcoholic fatty liver disease (NAFLD), which becomes a significant health problem worldwide. Lifestyle changes, however, affect not only parental generation, but also their offspring, rein...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2019.11.015
更新日期：2020-02-01 00:00:00
abstract：BACKGROUND:Plasma insulin levels are predominantly the product of the morphological mass of insulin producing beta cells in the pancreatic islets of Langerhans and the functional status of each of these beta cells. Thus, deficiency in either beta cell mass or function, or both, can lead to insufficient levels of insuli...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2017.06.019
更新日期：2017-07-08 00:00:00
abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a known regulator of central metabolic signaling, and mice with whole brain-, leptin receptor (LepRb) expressing cell-, or proopiomelanocortin neuron-specific PTP1B-deficiency are lean, leptin hypersensitive, and display improved glucose homeostasis. However, whether the meta...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.01.008
更新日期：2014-01-19 00:00:00
abstract：:Decreased β-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore β-cell mass and normoglycemia is to improve β-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2012.08.006
更新日期：2012-08-17 00:00:00
abstract：OBJECTIVE:Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.12.014
更新日期：2018-03-01 00:00:00
abstract：OBJECTIVES:Hepatic insulin resistance is a hallmark of type 2 diabetes and obesity. Insulin receptor signaling through AKT and FOXO has important metabolic effects that have traditionally been ascribed to regulation of gene expression. However, whether all the metabolic effects of FOXO arise from its regulation of prot...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.08.003
更新日期：2018-11-01 00:00:00
abstract：OBJECTIVE:Leptin is a cytokine produced by adipose tissue that acts mainly on the hypothalamus to regulate appetite and energy homeostasis. Previous studies revealed that the leptin receptor is expressed not only in neurons, but also in glial cells. Microglia are resident immune cells in the brain that play an essentia...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.11.003
更新日期：2018-01-01 00:00:00
abstract：OBJECTIVE:Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incompletely understood mechan...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.08.006
更新日期：2019-10-01 00:00:00
abstract：BACKGROUND/OBJECTIVES:Nuclear peroxisome proliferator activated receptor-α (PPAR-α) plays a fundamental role in the regulation of lipid homeostasis and is the target of medications used to treat dyslipidemia. However, little is known about the role of PPAR-α in mouse behavior. METHODS:To investigate the function of Pp...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.04.005
更新日期：2015-05-02 00:00:00
abstract：BACKGROUND:Diabetes is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of preventive and therapeutic approaches. Genetic and environmental factors are the culprits involved in diabetes risk. Evidence from the last decade has highli...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.101041
更新日期：2020-11-01 00:00:00
abstract：OBJECTIVE:Glucagon-like peptide 1 (GLP-1) enhances insulin secretion and protects β-cell mass. Diabetes therapies targeting the GLP-1 receptor (GLP-1R), expressed in numerous tissues, have diminished dose-response in patients with type 2 diabetes compared with healthy human controls. The aim of this study was to determ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.01.010
更新日期：2015-02-03 00:00:00
abstract：OBJECTIVE:The cocaine- and amphetamine-regulated transcript (CART) codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been r...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.10.015
更新日期：2018-01-01 00:00:00
abstract：OBJECTIVE:Nonalcoholic steatohepatitis (NASH) is closely associated with metabolic syndrome and increases the risk for end-stage liver disease, such as cirrhosis and hepatocellular carcinoma. Despite this, the molecular events that influence NASH pathogenesis remain poorly understood. The objectives of the current stud...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.12.004
更新日期：2019-02-01 00:00:00
abstract：OBJECTIVE:α/β-Hydrolase domain-6 (ABHD6) is a newly identified monoacylglycerol (MAG) lipase. We recently reported that it negatively regulates glucose stimulated insulin secretion (GSIS) in the β cells by hydrolyzing lipolysis-derived MAG that acts as a metabolic coupling factor and signaling molecule via exocytotic r...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.09.012
更新日期：2015-10-08 00:00:00
abstract：OBJECTIVE:T cell activation triggers metabolic reprogramming to meet increased demands for energy and metabolites required for cellular proliferation. Ethanolamine phospholipid synthesis has emerged as a regulator of metabolic shifts in stem cells and cancer cells, which led us to investigate its potential role during ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2021.101170
更新日期：2021-01-20 00:00:00
abstract：OBJECTIVE:Fasting results in major metabolic changes including a switch from glycogenolysis to gluconeogenesis to maintain glucose homeostasis. However, the relationship between the length of fasting and the relative contribution of gluconeogenic substrates remains unclear. We investigated the relative contribution of ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.11.005
更新日期：2020-01-01 00:00:00
abstract：OBJECTIVE:Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS:To i...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.07.015
更新日期：2017-10-01 00:00:00
abstract：OBJECTIVE:We tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). METHODS:Muscle biopsies were collected to determine differences in autophagy an...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.10.006
更新日期：2017-12-01 00:00:00
abstract：:Cytokine signaling has been connected to regulation of metabolism and energy balance. Numerous cytokine gene expression changes are stimulated by accumulation of bile acids in livers of young Foxa2 liver-conditional null mice. We hypothesized that bile acid-induced inflammation in young Foxa2 mutants, once chronic, af...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2013.08.005
更新日期：2013-08-24 00:00:00
abstract：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 u...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101129
更新日期：2020-11-25 00:00:00
abstract：OBJECTIVE:Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signal...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.05.006
更新日期：2017-05-15 00:00:00
abstract：OBJECTIVE:Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These 'BRITE/beige' a...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.02.006
更新日期：2015-03-03 00:00:00
abstract：OBJECTIVE:A major challenge for obesity treatment is the maintenance of reduced body weight. Diet-induced obese mice are resistant to achieving normoweight once the obesogenic conditions are reversed, in part because lowered circulating leptin leads to a reduction in metabolic rate and a rebound of hyperphagia that def...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.07.012
更新日期：2016-08-05 00:00:00
abstract：OBJECTIVE:Obesity is an enormous burden for patients and health systems world-wide. Brown adipose tissue dissipates energy in response to cold and has been shown to be metabolically active in human adults. The type I transforming growth factor β (TGFβ) receptor Activin receptor-like kinase 7 (Alk7) is highly expressed ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.06.003
更新日期：2015-06-14 00:00:00
abstract：OBJECTIVES:IL-13 is a cytokine classically produced by anti-inflammatory T-helper-2 lymphocytes; it is decreased in the circulation of type 2 diabetic patients and impacts positively on liver and skeletal muscle. Although IL-13 can exert positive effects on beta-cell lines, its impact and mode of action on primary beta...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.11.003
更新日期：2015-11-17 00:00:00
abstract：OBJECTIVE:Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) an...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.12.005
更新日期：2018-02-01 00:00:00
