scholarly journals Reduced ATGL-mediated lipolysis attenuates β-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue

2016 ◽  
Vol 311 (2) ◽  
pp. C269-C276 ◽  
Author(s):  
Rebecca E. K. MacPherson ◽  
Steven M. Dragos ◽  
Sofhia Ramos ◽  
Charles Sutton ◽  
Scott Frendo-Cumbo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Regulation Of Gene Expression ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Mitochondrial Content ◽  
Ampk Signaling ◽  
Cl 316,243 ◽  
Fatty Acid Release ◽  
Adipose Tissue Triglyceride

5′-AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis and has been shown to play a role in regulation of adipose tissue mitochondrial content. Conversely, the inhibition of lipolysis has been reported to potentiate the induction of protein kinase A (PKA)-targeted genes involved in the regulation of oxidative metabolism. The purpose of the current study was to address these apparent discrepancies and to more fully examine the relationship between lipolysis, AMPK, and the β-adrenergic-mediated regulation of gene expression. In 3T3-L1 adipocytes, the adipose tissue triglyceride lipase (ATGL) inhibitor ATGListatin attenuated the Thr172 phosphorylation of AMPK by a β3-adrenergic agonist (CL 316,243) independent of changes in PKA signaling. Similarly, CL 316,243-induced increases in the Thr172 phosphorylation of AMPK were reduced in adipose tissue from whole body ATGL-deficient mice. Despite reductions in the activation of AMPK, the induction of PKA-targeted genes was intact or, in some cases, increased. Similarly, markers of mitochondrial content and respiration were increased in adipose tissue from ATGL knockout mice independent of changes in the Thr172 phosphorylation of AMPK. Taken together, our data provide evidence that AMPK is not required for the regulation of adipose tissue oxidative capacity in conditions of reduced fatty acid release.

scholarly journals Evidence for fatty acids mediating CL 316,243-induced reductions in blood glucose in mice

2014 ◽  
Vol 307 (7) ◽  
pp. E563-E570 ◽  
Author(s):  
Rebecca E. K. MacPherson ◽  
Laura Castellani ◽  
Marie-Soleil Beaudoin ◽  
David C. Wright
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Blood Glucose ◽  
Interleukin 6 ◽  
Whole Body ◽  
Glucose Levels ◽  
Cl 316,243 ◽  
Plasma Insulin Levels ◽  
Adipose Tissue Triglyceride ◽  
Diabetes Drug

CL 316,243, a β3-adrenergic agonist, was developed as an antiobesity and diabetes drug and causes rapid decreases in blood glucose levels in mice. The mechanisms mediating this effect have not been fully elucidated; thus, the purpose of the current study was to examine the role of fatty acids and interleukin-6, reputed mediators of insulin secretion, in this process. To address this question, we used physiological and pharmacological approaches in combination with knockout mouse models. CL 316,243 treatment in male C57BL6 mice increased plasma fatty acids, glycerol, interleukin-6, and insulin and reduced blood glucose concentrations 2 h following injections. The ability of CL 316,243 to increase insulin and fatty acids and reduce glucose was preserved in interleukin-6-deficient mice. CL 316,243-induced drops in blood glucose occurred in parallel with increases in circulating fatty acids but prior to increases in plasma interleukin-6. CL 316,243-mediated increases in plasma insulin levels and reductions in blood glucose were attenuated when mice were pretreated with the lipase inhibitor nicotinic acid or in whole body adipose tissue triglyceride lipase knockout mice. Collectively, our findings demonstrate an important role for fatty acids in mediating the effects of CL 316,243 in mice. Not only do our results provide new insight into the mechanisms of action of CL 316,243, but they also hint at an unappreciated aspect of adipose tissue -pancreas cross-talk.

scholarly journals The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Jamie I. van der van der Vaart ◽  
Mariëtte R. Boon ◽  
Riekelt H. Houtkooper
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Ampk Signaling ◽  
Mitochondrial Homeostasis ◽  
Brown Adipose ◽  
Metabolic Stresses ◽  
Amp Activated Protein Kinase ◽  
Body Energy

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training

2014 ◽  
Vol 114 (7) ◽  
pp. 1463-1471 ◽  
Author(s):  
Malin Alvehus ◽  
Niklas Boman ◽  
Karin Söderlund ◽  
Michael B. Svensson ◽  
Jonas Burén
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Resistance Training ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Metabolic Adaptations

scholarly journals Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin

2007 ◽  
Vol 92 (7) ◽  
pp. 2688-2695 ◽  
Author(s):  
Giuseppe Murdolo ◽  
Ann Hammarstedt ◽  
Madeléne Sandqvist ◽  
Martin Schmelz ◽  
Christian Herder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Regulation Of Gene Expression ◽  
Whole Body ◽  
Mrna Levels ◽  
Abdominal Adipose Tissue ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Adipose Organ

Abstract Context: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in obesity-associated chronic inflammation, insulin resistance, and atherosclerosis. Objectives: The objectives of this study were to: 1) characterize the interstitial levels and the gene expression of MCP-1 in the sc abdominal adipose tissue (SCAAT), 2) elucidate the response of MCP-1 to acute hyperinsulinemia, and 3) determine the relationship between MCP-1 and arterial stiffness. Design: Nine lean (L) and nine uncomplicated obese (OB) males were studied in the fasting state and during a euglycemic-hyperinsulinemic clamp combined with the microdialysis technique. Interstitial and serum MCP-1 (iMCP-1 and sMCP-1, respectively) levels, pulse wave analysis, and SCAAT biopsies were characterized at baseline and after hyperinsulinemia. Results: OB showed elevated sMCP-1 (P < 0.01) but similar iMCP-1 levels as compared with L. Basal iMCP-1 concentrations were considerably higher than sMCP-1 (P < 0.0001), and a gradient between iMCP-1 and sMCP-1 levels was maintained throughout the hyperinsulinemia. At baseline, SCAAT gene expression profile revealed a “co-upregulation” of MCP-1, MCP-2, macrophage inflammatory protein-1α, and CD68 in OB, and whole-body glucose disposal inversely correlated with the MCP-1 gene expression. After hyperinsulinemia, MCP-1 and MCP-2 mRNA levels significantly increased in L, but not in OB. Finally, sMCP-1 excess in the OB positively correlated with the stiffer vasculature. Conclusions: These observations demonstrate similar interstitial concentrations and a differential gene response to hyperinsulinemia of MCP-1 in the SCAAT from L and OB individuals. In human obesity, we suggest the SCAAT MCP-1 gene overexpression as a biomarker of an “inflamed” adipose organ and impaired glucose metabolism.

scholarly journals AMP-activated protein kinase (AMPK) contributes to the anti-obesity effects and adipose tissue browning of alpha-lipoic acid in ovariectomized rats

2021 ◽  
Author(s):  
Hsin-Hsueh Shen ◽  
Ming-Ting Chung ◽  
Shieh-Yang Huang ◽  
Ching-Wen Kung ◽  
Shu-Ying Chen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Lipoic Acid ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Ampk Signaling ◽  
Ovx Rats ◽  
Beige Adipocytes ◽  
Amp Activated Protein Kinase ◽  
Tissue Browning

Abstract BackgroundBilateral ovariectomy is an experimental model used to analyze the conditions of menopause and develop strategies for alleviation of the deleterious effects during estrogen deficiency. Brown and beige adipocytes exert thermogenesis capacities and are promising therapeutic strategy for obesity. This study aims to investigate the adipose tissue browning potentials of antioxidant α-lipoic acid (ALA) and underlying mechanisms involved in ovariectomized (Ovx) rats.Methods:Eight weeks old female Wistar rats were randomly divided into Sham or Ovx groups. The Ovx rats were subjected to bilateral ovariectomy and administered with ALA 200 or ALA 300 mg/kg/day (gavage) for 8 weeks. Results:Ovx group significantly increased boy weight (BW) and fat pad mass as compared to Sham group, while ALA supplementation reversed these changes. Lipid profiles including serum triglycerides (TG), total (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated in the Ovx group, whereas the ALA treatment showed a significant decrease in these levels. Furthermore, high density lipoprotein cholesterol (HDL-C) and myokine irisin secretion were increased by ALA as well. Morphology results showed ALA treatment reduced Ovx-induced adipocyte hypertrophy and enhanced UCP1 expression by immunohistochemical staining in inguinal WAT. Protein expression of brown fat-specific markers UCP1, PRDM16 and CIDEA was markedly reduced in Ovx rats, whereas ALA treatment reversed these changes. ALA significantly increased liver kinase B1 (LKB1) and phosphorylation of AMP-activated protein kinase (AMPK) and the downstream acetyl-CoA carboxylase (ACC) that were decreased by Ovx, suggesting the browning effects were mediated by AMPK signaling. Conclusions:ALA ameliorates obesity caused by hormone deprivation in menopause via conversion of white to beige adipocytes concomitant with the activation of AMPK signaling.

β-Lapachone Regulates Obesity through Modulating Thermogenesis in Brown Adipose Tissue and Adipocytes: Role of AMPK Signaling Pathway

2019 ◽  
Vol 47 (04) ◽  
pp. 803-822 ◽  
Author(s):  
Hyun Jeong Kwak ◽  
Mi-Young Jeong ◽  
Jae-Young Um ◽  
Jinbong Park
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Brown Adipose Tissue ◽  
Signaling Pathway ◽  
Uncoupling Protein ◽  
Therapeutic Implication ◽  
Mitogen Activated Protein Kinase ◽  
Ampk Signaling ◽  
Compound C ◽  
Brown Adipose

Activation of brown adipose tissue (BAT) has been proposed as a promising target against obesity due to its increased capacity for thermogenesis. In this study, we explored the effect of [Formula: see text]-Lapachone ([Formula: see text]L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of [Formula: see text]L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr[Formula: see text] mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). In addition, [Formula: see text]L elevated thermogenic proteins including uncoupling protein 1 (UCP1) and mitochondrial count in BAT and human adipose tissue-derived mesenchymal stem cells (hAMSCs). [Formula: see text]L also induced AMP-activated protein kinase (AMPK) phosphorylation, subsequent upregulation of acetyl-CoA carboxylase (ACC) and UCP1, and these effects were diminished by AMPK inhibitor compound C, suggesting that AMPK underlies the effects of [Formula: see text]L. Mitogen-activated protein kinase pathways participated in the thermogenesis of [Formula: see text]L, specifically p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated by [Formula: see text]L treatment in hAMSCs. Additionally, inhibitors of p38/JNK/ERK1/2 abrogated the activity of [Formula: see text]L. Taken together, [Formula: see text]L exerts anti-obese effects by inducing thermogenesis mediated by AMPK signaling pathway, suggesting that [Formula: see text]L may have a potential therapeutic implication of obesity. Taken together, [Formula: see text]L exerts anti-obese effects by not only inducing thermogenesis on brown adipocytes but also inducing the browning of white adipocytes. The anti-obese effect of [Formula: see text]L is mediated by AMPK signaling pathway, suggesting that [Formula: see text]L may have potential therapeutic implication of obesity.

scholarly journals Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Craig Porter ◽  
Elisabet Børsheim ◽  
Labros S. Sidossis
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Brown Adipose Tissue ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Research Strategies ◽  
Brown Adipocytes ◽  
Brown Adipose

The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies.

scholarly journals STK25 regulates oxidative capacity and metabolic efficiency in adipose tissue

2018 ◽  
Vol 238 (3) ◽  
pp. 187-202 ◽  
Author(s):  
Silva Sütt ◽  
Emmelie Cansby ◽  
Alexandra Paul ◽  
Manoj Amrutkar ◽  
Esther Nuñez-Durán ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Oxidative Capacity ◽  
Dietary Lipids ◽  
Lipid Storage ◽  
Whole Body ◽  
Mitochondrial Activity ◽  
Metabolic Efficiency ◽  
High Fat ◽  
Inflammatory Infiltration

Whole-body energy homeostasis at over-nutrition critically depends on how well adipose tissue remodels in response to excess calories. We recently identified serine/threonine protein kinase (STK)25 as a critical regulator of ectopic lipid storage in non-adipose tissue and systemic insulin resistance in the context of nutritional stress. Here, we investigated the role of STK25 in regulation of adipose tissue dysfunction in mice challenged with a high-fat diet. We found that overexpression of STK25 in high-fat-fed mice resulted in impaired mitochondrial function and aggravated hypertrophy, inflammatory infiltration and fibrosis in adipose depots. Reciprocally, Stk25-knockout mice displayed improved mitochondrial function and were protected against diet-induced excessive fat storage, meta-inflammation and fibrosis in brown and white adipose tissues. Furthermore, in rodent HIB-1B cell line, STK25 depletion resulted in enhanced mitochondrial activity and consequently, reduced lipid droplet size, demonstrating an autonomous action for STK25 within adipocytes. In summary, we provide the first evidence for a key function of STK25 in controlling the metabolic balance of lipid utilization vs lipid storage in brown and white adipose depots, suggesting that repression of STK25 activity offers a potential strategy for establishing healthier adipose tissue in the context of chronic exposure to dietary lipids.

scholarly journals Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content

2021 ◽  
Vol 9 ◽  
Author(s):  
Natalie Burchat ◽  
Priyanka Sharma ◽  
Hong Ye ◽  
Sai Santosh Babu Komakula ◽  
Agnieszka Dobrzyn ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Whole Body ◽  
Chow Diet ◽  
Maternal Transmission ◽  
Mitochondrial Content ◽  
Diet Induced Obesity ◽  
Body Energy ◽  
Obesity Resistance

Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese (Ay/a) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in Ay/a mice (Ay/aTg) prevents increased body weight, without reducing food intake. Instead, obesity resistance in Ay/aTg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the Ay/a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring.

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