M1-M2 balancing act in white adipose tissue browning – a new role for RIP140

Liu, Pu Ste; Lin, Yi; Burton, Frank H.; Wei, Li‐Na

doi:10.4161/21623945.2014.981428

Cited by 22 publications

(19 citation statements)

References 20 publications

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“…The signature uncoupling protein of BAT, UCP-1, was not significantly altered by either intervention. Since recent evidence implicates alternative (i.e., M2) macrophage activity with AT browning (24) and exercise is known to shift macrophages toward M2 (18), the alternative macrophage-polarizing cytokine, IL-13, as well as the M2 macrophage marker, C-type mannose receptor-1 (MRC1), were measured. Interestingly, both genes were found to be higher in the treatment groups, although the diet-induced increase in MRC1 was not statistically significant ( Figure 2F ).…”

Section: Resultsmentioning

confidence: 99%

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Welly

Liu

Zidon

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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Cardiometabolic impairments that begin early in life are particularly critical, as they often predict metabolic dysfunction into adulthood. Obesity, high-fat diet (HFD), and inactivity are all associated with adipose tissue (AT) inflammation and insulin resistance (IR), major predictors of metabolic dysfunction. Recent evidence also has associated the gut microbiome with cardiometabolic health. PURPOSE Compare equal energy deficits induced by exercise and caloric reduction on cardiometabolic disease risk parameters including AT inflammation, IR and gut microbiota changes during HFD consumption. METHODS Obesity-prone rats fed HFD were exercise trained (Ex, n=10) or weight-matched to Ex via caloric reduction while kept sedentary (WM, n=10), and compared to ad libitum HFD-fed (Sed, n=10) rats for IR, systemic energetics and spontaneous physical activity (SPA), adiposity, and fasting metabolic parameters. Visceral, subcutaneous, periaortic, and brown AT, liver, aorta, and cecal digesta were examined. RESULTS Despite identical reductions in adiposity, Ex, but not WM, improved IR, increased SPA by ~26% (p<0.05 compared to WM and Sed), and reduced LDL cholesterol (p<0.05 compared to Sed). WM and Ex both reduced inflammatory markers in all AT depots and aorta, while only Ex increased indicators of mitochondrial function in brown AT. Ex significantly increased the relative abundance of cecal Streptococcaceae and decreased S24-7 and one undefined genus in Rikenellacea; WM induced similar changes that did not reach statistical significance. CONCLUSIONS Both Ex and WM reduced AT inflammation across depots, while Ex caused more robust changes to gut microbial communities, improved IR, increased fat oxidation, increased SPA, and increased indices of brown AT mitochondrial function. Our findings add to the growing body of literature indicating that there are weight-loss independent metabolic benefits of exercise.

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Section: Resultsmentioning

confidence: 99%

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Welly

Liu

Zidon

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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“…Whereas acute exercise increased circulating and skeletal muscle FGF21 levels in some studies (Hansen, et al 2016; Kim et al 2013; Slusher, et al 2015; Tanimura et al 2016), it induced no change or a reduction in circulating FGF21 in others (Taniguchi, et al 2016). Thus, its role in exercise-mediated browning of WAT (Stanford et al 2015), a process associated with both reduced inflammation (Liu, et al 2015) and increased mitochondrial function (Bae, et al 2014), requires further investigation. Here, we tested whether FGF21 is required for exercise-mediated immunometabolic adaptations in adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21

Porter

Rowles

Fletcher

et al. 2017

Journal of Endocrinology

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Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly-defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies. Thus, the role that FGF21 plays in mediating the positive metabolic effects of exercise in AT are unclear. In this study, FGF21 knock-out (KO) mice were used to directly assess the role of FGF21 in mediating the metabolic and anti-inflammatory effects of exercise on white AT (WAT) and brown AT (BAT). Male FGF21KO and wild-type mice were provided running wheels or remained sedentary for 8 weeks (n=9–15/group) and compared for adiposity, insulin sensitivity (i.e., HOMA-IR, Adipo-IR), and AT inflammation and metabolic function (e.g., mitochondrial enzyme activity, subunit content). Adiposity and Adipo-IR were increased in FGF21KO mice and decreased by EX. The BAT of FGF21KO animals had reduced mitochondrial content and decreased relative mass, both normalized by EX. WAT and BAT inflammation was elevated in FGF21KO mice, reduced in both genotypes by EX. EX increased WAT Pgc1alpha gene expression, citrate synthase activity, COX I content, and total AMPK content in WT but not FGF21KO mice. Collectively, these findings reveal a previously unappreciated anti-inflammatory role for FGF21 in WAT and BAT, but do not support that FGF21 is necessary for EX-mediated anti-inflammatory effects.

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“…Treatment with a β3-adrenergic agonist triggers the death of numerous unilocular white adipocytes, followed by clearance of the dead fat cells (eff erocytosis) by resident macrophages that assume an M2 phenotype and a subsequent brown/ beige adipogenesis in gonadal white adipose tissue (Lee et al 2012;. Liu et al (2015) have shown that receptor Interacting Protein 140 (RIP140) may play a key role in regulating the balance of M1/M2 macrophages in the white adipose tissue. Lowering the level of RIP140 in macrophages reduces M1 macrophages, while it expands anti-infl ammatory M2 macrophages, triggering WAT "browning", fat burning, and restoration of insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats

Vargovič

Manz²,

Květňanský

2016

Endocrine Regulations

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Objective. Continuous exposure to cold leads to an activation of adaptive thermogenesis in the brown adipose tissue and induction of brown/beige cell phenotype in the white adipose tissue. Th ermogenic response is associated with alternatively activated macrophages producing catecholamines, which subsequently activate the uncoupling protein 1 (UCP-1). Th e aim of this work was to elucidate the eff ect of cold exposure on catecholamine and immune responses associated with adipocyte browning in the mesenteric adipose tissue (mWAT) of rat.Methods. Th e rats were exposed to continuous cold (4 °C) for 1 or 7 days. Catecholamines production and gene expressions of infl ammatory and other factors, related to adipocyte "browning", were analyzed in the homogenized mWAT samples using 2-CAT ELISA kits.Results. Cold exposure induced a sympathetic response in the mWAT, evidenced by the tyrosine hydroxylase (TH) protein level rise. Induction of non-sympathetical catecholamine production was observed 7 days aft er cold exposure by elevated TH and phenylethanolamine-N-methyltransferase (PNMT) expression, leading to an increased epinephrine levels. Cold exposure for 7 days stimulated the infi ltration of macrophages, evaluated by F4/80 and CD68 expressions, and expression of anti-infl ammatory mediators, while pro-infl ammatory cytokines were inhibited. Anti-infl ammatory response, accompanied by de novo catecholamine production and up-regulation of β3-adrenergic receptors, led to the stimulation of UCP-1 and PGC1α expression, suggesting a cold-induced "browning" of the mWAT, mediated by alternatively activated macrophages.Conclusions. Th e present data indicate that prolonged cold exposure may induce anti-infl ammatory response in mWAT associated with induction of UCP-1 expression. Although functional thermogenesis in the mWAT is most likely redundant, a highly effi cient dissipation of energy by UCP1 may aff ect the energy homeostasis in this visceral fat.

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M1-M2 balancing act in white adipose tissue browning – a new role for RIP140

Cited by 22 publications

References 20 publications

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21

Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats

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