Abstract：
OBJECTIVE:Identification of additional regulatory factors involved in the onset of obesity is important to understand the mechanisms underlying this prevailing disease and its associated metabolic disorders and to develop therapeutic strategies. Through isolation and analysis of a mutant, we aimed to uncover the function of a Ras-GAP gene, Rasal2 (Ras protein activator like 2), in the development of obesity and related metabolic disorders and to obtain valuable insights regarding the mechanism underlying the function. METHODS:An obesity-based genetic screen was performed to identify an insertional mutation that disrupts the expression of Rasal2 (Rasal2 PB/PB mice). Important metabolic parameters, such as fat mass and glucose tolerance, were measured in Rasal2 PB/PB mice. The impact of Rasal2 on adipogenesis was evaluated in the mutant mice and in 3T3-L1 preadipocytes treated with Rasal2 siRNA. Ras and ERK activities were then evaluated in Rasal2-deficient preadipocytes or mice, and their functional relationships with Rasal2 on adipogenesis were investigated by employing Ras and MEK inhibitors. RESULTS:Rasal2 PB/PB mice showed drastic decrease in Rasal2 expression and a lean phenotype. The mutant mice displayed decreased adiposity and resistance to high-fat diet induced metabolic disorders. Further analysis indicated that Rasal2 deficiency leads to impaired adipogenesis in vivo and in vitro. Moreover, while Rasal2 deficiency resulted in increased activity of both Ras and ERK in preadipocytes, reducing Ras, but not ERK, suppressed the impaired adipogenesis. CONCLUSIONS:Rasal2 promotes adipogenesis, which may critically contribute to its role in the development of obesity and related metabolic disorders and may do so by repressing Ras activity in an ERK-independent manner.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Zhu X,Xie S,Xu T,Wu X,Han Mdoi
10.1016/j.molmet.2017.03.003subject
Has Abstractpub_date
2017-03-18 00:00:00pages
494-502issue
6issn
2212-8778pii
S2212-8778(17)30125-4journal_volume
6pub_type
杂志文章abstract：OBJECTIVE:Clear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPARγ), detected in both ccRCC tumors and cell...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.05.013
更新日期：2018-08-01 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：OBJECTIVE:α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying b...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.01.003
更新日期：2017-01-12 00:00:00
abstract：:Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in hum...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2013.12.001
更新日期：2013-12-14 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: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: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：OBJECTIVE AND METHODS:Metabolic viscera and their vasculature are richly innervated by peripheral sensory neurons. Here, we examined the metabolic and inflammatory profiles of mice with selective ablation of all Nav1.8-expressing primary afferent neurons. RESULTS:While mice lacking sensory neurons displayed no differe...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2017.07.012
更新日期：2017-10-01 00:00:00
abstract：OBJECTIVES:We quantified the effect of environmental temperature on mouse energy homeostasis and body temperature. METHODS:The effect of environmental temperature (4-33 °C) on body temperature, energy expenditure, physical activity, and food intake in various mice (chow diet, high-fat diet, Brs3 (-/y) , lipodystrophic...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.03.001
更新日期：2015-03-10 00:00:00
abstract：OBJECTIVE:Glucose promotes lipid remodelling in pancreatic β-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. METHODS:Using mass spectrometry (MS) we quantified changes in approximately 300...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.04.003
更新日期：2016-04-13 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：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:Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.03.014
更新日期：2018-06-01 00:00:00
abstract：OBJECTIVES:Nutrient sensing by hypothalamic neurons is critical for the regulation of food intake and energy expenditure. We aimed to identify long- and medium-chain fatty acid species transported into the brain, their effects on energy balance, and the mechanisms by which they regulate activity of hypothalamic neurons...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.01.002
更新日期：2020-04-01 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：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 strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.11.010
更新日期：2018-02-01 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:A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work su...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.03.012
更新日期：2017-04-26 00:00:00
abstract：OBJECTIVE:The liver performs a central role in regulating energy homeostasis by increasing glucose output during fasting. Recent studies on Argonaute2 (Ago2), a key RNA-binding protein mediating the microRNA pathway, have illustrated its role in adaptive mechanisms according to changes in metabolic demand. Here we soug...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.10.003
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:In addition to their crucial role in reproduction, estrogens are key regulators of energy and glucose homeostasis and they also exert several cardiovascular protective effects. These beneficial actions are mainly mediated by estrogen receptor alpha (ERα), which is widely expressed in metabolic and vascular t...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2018.05.009
更新日期：2018-09-01 00:00:00
abstract：OBJECTIVE:Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested that impairment of FGF21 signaling in adipose tissue may occur through downregulation of the obligate FGF21 co-receptor, β-klotho, which leads to "FGF21 resistance" during the onset of...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.03.009
更新日期：2017-03-27 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:Enteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake and storage. Our goal is to decipher the gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context,...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.08.007
更新日期：2019-11-01 00:00:00
abstract：OBJECTIVE:Pharmacological activation of adenosine signaling has been shown to increase β-cell proliferation and thereby β-cell regeneration in zebrafish and rodent models of diabetes. However, whether adenosine has an endogenous role in regulating β-cell proliferation is unknown. The objective of this study was to dete...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.09.006
更新日期：2016-09-20 00:00:00
abstract：BACKGROUND:GPRC6A, a widely expressed G-protein coupled receptor, is proposed to be a master regulator of complex endocrine networks and metabolic processes. GPRC6A is activated by multiple ligands, including osteocalcin (Ocn), testosterone (T), basic amino acids, and various cations. SCOPE OF REVIEW:We review the con...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2016.12.006
更新日期：2016-12-21 00:00:00
abstract：OBJECTIVE:Mice with congenital loss of the glucagon receptor gene (Gcgr-/- mice) remain normoglycemic in insulinopenic conditions, suggesting that unopposed glucagon action is the driving force for hyperglycemia in Type-1 Diabetes Mellitus (T1DM). However, chronic loss of GCGR results in a neomorphic phenotype that inc...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.07.012
更新日期：2018-11-01 00:00:00
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' ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.05.006
更新日期：2018-07-01 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：: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
