Acute Stimulation of White Adipocyte Respiration by PKA-Induced Lipolysis

Yehuda‐Shnaidman, Einav; Buehrer, Benjamin M.; Pi, Jingbo; Kumar, Naresh; Collins, Sheila

doi:10.2337/db10-0245

Cited by 102 publications

(110 citation statements)

References 53 publications

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“…However in human, obesity is associated with reduced RIIβ expression and PKA activity in WAT (Mantovani et al 2009). βAR-stimulated lipolysis and mitochondrial respiration are also decreased in WAT of obese patients (Yehuda-Shnaidman et al 2010). In 3T3-L1 adipocytes, it has been shown that the anchoring of PKA to AKAP is required for βAR-stimulated lipolysis (Pidoux et al 2011).…”

Section: Camp/pka In Adipose Tissuesmentioning

confidence: 99%

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

Yang

2016

Journal of Molecular Endocrinology

151

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In mammals, cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is usually elicited by binding of hormones and neurotransmitters to G protein-coupled receptors (GPCRs). cAMP exerts many of its physiological effects by activating cAMPdependent protein kinase (PKA), which in turn phosphorylates and regulates the functions of downstream protein targets including ion channels, enzymes, and transcription factors. cAMP/PKA signaling pathway regulates glucose homeostasis at multiple levels including insulin and glucagon secretion, glucose uptake, glycogen synthesis and breakdown, gluconeogenesis, and neural control of glucose homeostasis. This review summarizes recent genetic and pharmacological studies concerning the regulation of glucose homeostasis by cAMP/PKA in pancreas, liver, skeletal muscle, adipose tissues, and brain. We also discuss the strategies for targeting cAMP/PKA pathway for research and potential therapeutic treatment of type 2 diabetes mellitus (T2D).

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Section: Camp/pka In Adipose Tissuesmentioning

confidence: 99%

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

Yang

2016

Journal of Molecular Endocrinology

151

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“…12,17,18 Studies of cachexia in rodents suggest activation of thermogenesis (i.e., increased mitochondrial uncoupling of oxidative phosphorylation and elevated fatty acid b-oxidation) in brown adipose tissue 19,20 may contribute to elevated whole body lipid utilization in cachexia, at least in later stages of cachexia. 20 Additionally, recent studies in healthy rodents and human adipocytes have linked stimulation of lipolysis in white adipose tissue with increased fatty acid oxidation 21,22 and uncoupling 21,23,24 in white adipose depots. This "brown-like" adipocyte phenotype in white adipose tissue might also contribute to elevated whole body lipid utilization in cachexia and thus depletion of adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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Keywords: colon-26 adenocarcinoma, early cachexia, energy expenditure, lipid metabolism, lipolysis, thermogenesis Abbreviations: eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; iBAT, interscapular brown adipose tissue; PKA, protein kinase A; ATGL, adipose triglyceride lipase; HSL, hormone sensitive lipase; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; PGC, peroxisome proliferator activated receptor gamma coactivator; CPT, carnitine palmitoyltransferase; DIO, iodothyronine deiodinase; MuRF, muscle ring finger protein; COX, cytochrome c oxidase subunits; GYK, glycerokinase; PRDM, PR domain zinc finger protein; ACOX, acyl CoA oxidase; CRP, C-reactive protein; LPL, lipoprotein lipase; H&E, hematoxylin and eosin; TEE, total energy expenditure; RER, respiratory exchange ratio.Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia -before severe fat loss -in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A -activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

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“…When (post)prandial plasma levels of NEFA and triacylglycerol (TG) exceed the storage capacity of WAT [1], other tissues including the liver and muscle become overloaded with lipids, which results in insulin resistance, the key event in the pathophysiology of metabolic syndrome [2]. The important role of WAT in energy homeostasis is underscored by the findings that WAT is one of the key organs affected by calorie restriction, the most effective strategy to prolong a healthy life in several species [3], and by the fact that accumulation of body fat can be reduced through upregulation of lipid catabolism in WAT [4][5][6][7][8][9][10]. The metabolism and secretory functions of WAT are also modulated by longchain (LC) n-3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), which exert numerous beneficial effects on health, including improvements in lipid metabolism and prevention of obesity and diabetes [11], while decreasing the rate of fatal coronary heart disease in diabetic patients who have had a myocardial infarction [12].…”

Section: Introductionmentioning

confidence: 99%

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

et al. 2011

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Aims/hypothesis Calorie restriction is an essential component in the treatment of obesity and associated diseases. Longchain n-3 polyunsaturated fatty acids (LC n-3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC n-3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice. Methods Male mice (C57BL/6J) were habituated to a cornoil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC n-3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF+F), ad libitum; (3) cHF with calorie restriction (CR; cHF+CR); and (4) cHF+F+CR. Mice fed a chow diet were also studied. Results We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC n-3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ 12,15 -prostaglandin J 2 and protectin D1. Conclusions/interpretation White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC n-3 PUFA to improve therapeutic strategies for metabolic syndrome.

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Acute Stimulation of White Adipocyte Respiration by PKA-Induced Lipolysis

Cited by 102 publications

References 53 publications

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

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