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' adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as "browning." Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. METHODS:Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. RESULTS:RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. CONCLUSIONS:Upregulation of Nppb, Npr1, Npr2, and β3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Neinast MD,Frank AP,Zechner JF,Li Q,Vishvanath L,Palmer BF,Aguirre V,Gupta RK,Clegg DJdoi
10.1016/j.molmet.2015.02.006subject
Has Abstractpub_date
2015-03-03 00:00:00pages
427-36issue
5issn
2212-8778pii
S2212-8778(15)00042-3journal_volume
4pub_type
杂志文章abstract:OBJECTIVE:Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover, FFAs act via multip...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.02.001
更新日期:2016-02-13 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
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更新日期:2019-08-01 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::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:OBJECTIVE:Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steato...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.03.016
更新日期:2017-06-21 00:00:00
abstract:OBJECTIVE:The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt), a mitochondrial enzyme involved in NADPH production, which has been suggested to lead to glucose intolerance and beta-cell dysfunction. However, re...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.09.006
更新日期:2014-09-28 00:00:00
abstract:OBJECTIVE:Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.06.010
更新日期:2015-07-06 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2015.12.006
更新日期:2016-01-14 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.03.008
更新日期:2018-05-01 00:00:00
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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
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.06.002
更新日期:2018-08-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.04.010
更新日期:2019-07-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101145
更新日期:2020-12-19 00:00:00
abstract:BACKGROUND:Poly-ADP-ribose polymerases (PARPs) are key mediators of cellular stress response. They are intimately linked to cellular metabolism through the consumption of NAD+. PARP1/ARTD1 in the nucleus is the major NAD+ consuming activity and plays a key role in maintaining genomic integrity. SCOPE OF REVIEW:In this...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.01.014
更新日期:2020-08-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101052
更新日期:2020-11-01 00:00:00
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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
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101057
更新日期:2020-12-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.05.002
更新日期:2016-05-12 00:00:00
abstract: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 mainte...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2021.101165
更新日期:2021-01-14 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101144
更新日期:2020-12-18 00:00:00
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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::The lipin protein family of phosphatidate phosphatases has an established role in triacylglycerol synthesis and storage. Physiological roles for lipin-1 and lipin-2 have been identified, but the role of lipin-3 has remained mysterious. Using lipin single- and double-knockout models we identified a cooperative relation...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2013.11.008
更新日期:2013-11-28 00:00:00
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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: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::SIRT1 has attracted a lot of interest since it was discovered as a mammalian homolog of Sir2, a protein that influences longevity in yeast. Intensive early research suggested a key role of SIRT1 in mammalian development, metabolic flexibility and oxidative metabolism. However, it is the growing body of transgenic mode...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2013.10.006
更新日期:2013-10-23 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: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:BACKGROUND:The availability of human pancreatic islets with characteristics closely resembling those present in vivo is instrumental for ex vivo studies in diabetes research. SCOPE OF REVIEW:In this review we propose metabolically phenotyped surgical patients as a novel source of pancreatic tissue for islet research. ...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2019.06.006
更新日期:2019-09-01 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/METHODS:DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.11.003
更新日期:2016-11-16 00:00:00