scholarly journals Adiponectin Reverses the Hypothalamic Microglial Inflammation during Short-Term Exposure to Fat-Rich Diet

2019 ◽  
Vol 20 (22) ◽  
pp. 5738 ◽  
Author(s):  
Hannah Lee ◽  
Thai Hien Tu ◽  
Byong Seo Park ◽  
Sunggu Yang ◽  
Jae Geun Kim
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Short Term ◽  
Microglial Cell Line ◽  
Short Term Exposure ◽  
Hypothalamic Inflammation ◽  
Anti Inflammatory ◽  
Exogenous Treatment

Adiponectin, an adipokine derived from the adipose tissue, manifests anti-inflammatory effects in the metabolically active organs and is, therefore, beneficial in various metabolic diseases associated with inflammation. However, the role of adiponectin in alleviating the hypothalamic inflammation connected to the pathogenesis of obesity has not yet been clearly interrogated. Here, we identified that the systemic administration of adiponectin suppresses the activation of microglia and thereby reverses the hypothalamic inflammation during short-term exposure to a high-fat diet. Additionally, we show that adiponectin induces anti-inflammatory effects in the microglial cell line subjected to an exogenous treatment with a saturated free fatty acid. In conclusion, the current study suggests that adiponectin suppresses the saturated free fatty acid-triggered the hypothalamic inflammation by modulating the microglial activation and thus maintains energy homeostasis.

scholarly journals Free fatty acid receptor 4 is a nutrient sensor that resolves inflammation to maintain cardiac homeostasis

2019 ◽  
Author(s):  
Katherine A. Murphy ◽  
Brian A. Harsch ◽  
Chastity L. Healy ◽  
Sonal S. Joshi ◽  
Shue Huang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Cardiac Myocytes ◽  
Transcriptome Analysis ◽  
Pressure Overload ◽  
Plasma Lipoproteins ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
Anti Inflammatory ◽  
Fatty Acid Receptor

AbstractBackgroundNon-­resolving activation of immune responses is central to the pathogenesis of heart failure (HF). Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor (GPR) for medium-and long-chain fatty acids (FA) that regulates metabolism and attenuates inflammation in diabetes and obesity. Here, we tested the hypothesis that Ffar4 functions as a cardioprotective nutrient sensor that resolves inflammation to maintain cardiac homeostasis.MethodsMice with systemic deletion of Ffar4 (Ffar4KO) were subjected to pressure overload by transverse aortic constriction (TAC). Transcriptome analysis of cardiac myocytes was performed three days post-TAC. Additionally, Ffar4-mediated effects on inflammatory oxylipin production in cardiac myocytes and oxylipin composition in plasma lipoproteins were evaluated.ResultsIn Ffar4KO mice, TAC induced more severe remodeling, identifying an entirely novel cardioprotective role for Ffar4 in the heart. Transcriptome analysis 3-days post-TAC indicated a failure to induce cell death and inflammatory genes in Ffar4KO cardiac myocytes, as well as a specific failure to induce cytoplasmic phospholipase A2α (cPLA2α) signaling genes. In cardiac myocytes, Ffar4 signaling through cPLA2α-cytochrome p450 ω/ω-1 hydroxylase induced production of the EPA-derived anti-inflammatory oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Systemically, loss of Ffar4 altered oxylipin content in circulating plasma lipoproteins consistent with a loss of anti-inflammatory oxylipins at baseline, and inability to produce both pro-inflammatory and pro-resolving oxylipins following TAC. Finally, we confirmed that Ffar4 is expressed in human heart and down-regulated in HF.ConclusionsOur results identify a novel function for Ffar4 in the heart as a FA nutrient sensor that resolves inflammation to maintain cardiac homeostasis.

scholarly journals Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Clara Machado Campolim ◽  
Lais Weissmann ◽  
Clílton Kraüss de Oliveira Ferreira ◽  
Olivia Pizetta Zordão ◽  
Ana Paula Segantine Dornellas ◽  
...  
Keyword(s):  
Air Pollution ◽  
Leptin Resistance ◽  
Short Term ◽  
Short Term Exposure ◽  
Hypothalamic Inflammation

scholarly journals Free fatty acid receptor 2 and nutrient sensing: a proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation

2010 ◽  
Vol 23 (1) ◽  
pp. 135-145 ◽  
Author(s):  
Michelle L. Sleeth ◽  
Emily L. Thompson ◽  
Heather E. Ford ◽  
Sagen E. K. Zac-Varghese ◽  
Gary Frost
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Energy Homeostasis ◽  
Short Chain Fatty Acids ◽  
Nutrient Sensing ◽  
Obesity Prevalence ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
Fatty Acid Receptor

The way in which the composition of the diet may affect appetite, food intake and body weight is now receiving considerable attention in a bid to halt the global year-on-year rise in obesity prevalence. Epidemiological evidence suggests that populations who follow a fibre-rich, traditional diet are likely to have a lower body weight and improved metabolic parameters than their Western-diet counterparts. The colonic effects of fibre, and more specifically the SCFA that the fermentation process produces, may play a role in maintaining energy homeostasis via their action on the G-coupled protein receptor free fatty acid receptor 2 (FFA2; formerly GPR43). In the present review, we summarise the evidence for and against the role of FFA2 in energy homeostasis circuits and the possible ways that these could be exploited therapeutically. We also propose that the decline in fibre content of the diet since the Industrial Revolution, particularly fermentable fractions, may have resulted in the FFA2-mediated circuits being under-utilised and hence play a role in the current obesity epidemic.

Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis

2009 ◽  
Vol 89 (3-4) ◽  
pp. 82-88 ◽  
Author(s):  
Atsuhiko Ichimura ◽  
Akira Hirasawa ◽  
Takafumi Hara ◽  
Gozoh Tsujimoto
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Energy Homeostasis ◽  
Free Fatty Acid Receptors

scholarly journals Wnt-Lrp5 Signaling Regulates Fatty Acid Metabolism in the Osteoblast

2015 ◽  
Vol 35 (11) ◽  
pp. 1979-1991 ◽  
Author(s):  
Julie L. Frey ◽  
Zhu Li ◽  
Jessica M. Ellis ◽  
Qian Zhang ◽  
Charles R. Farber ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Bone Mass ◽  
Energy Homeostasis ◽  
Acid Metabolism ◽  
Plasma Triglyceride ◽  
High Bone Mass ◽  
Fate Specification ◽  
High Bone

The Wnt coreceptors Lrp5 and Lrp6 are essential for normal postnatal bone accrual and osteoblast function. In this study, we identify a previously unrecognized skeletal function unique to Lrp5 that enables osteoblasts to oxidize fatty acids. Mice lacking the Lrp5 coreceptor specifically in osteoblasts and osteocytes exhibit the expected reductions in postnatal bone mass but also exhibit an increase in body fat with corresponding reductions in energy expenditure. Conversely, mice expressing a high bone mass mutant Lrp5 allele are leaner with reduced plasma triglyceride and free fatty acid levels. In this context, Wnt-initiated signals downstream of Lrp5, but not the closely related Lrp6 coreceptor, regulate the activation of β-catenin and thereby induce the expression of key enzymes required for fatty acid β-oxidation. These results suggest that Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated with fate specification and differentiation in bone and that the skeleton influences global energy homeostasis via mechanisms independent of osteocalcin and glucose metabolism.

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