Fat poetry: a kingdom for PPARγ

Anghel, S; Wahli, Walter

doi:10.1038/cr.2007.48

Cited by 135 publications

(136 citation statements)

References 266 publications

(293 reference statements)

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“…The requirement for PPARγ is not unexpected, as adipogenic differentiation requires PPARγ activity (24). Our conclusions related to the requirement for EMT rest on several observations: adult heart injury induces EMT and induces fat when PPARγ is expressed (Fig.…”

Section: Discussionmentioning

confidence: 87%

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Yamaguchi

Cavallero

Patterson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

130

116

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The hearts of many mammalian species are surrounded by an extensive layer of fat called epicardial adipose tissue (EAT). The lineage origins and determinative mechanisms of EAT development are unclear, in part because mice and other experimentally tractable model organisms are thought to not have this tissue. In this study, we show that mouse hearts have EAT, localized to a specific region in the atrial–ventricular groove. Lineage analysis indicates that this adipose tissue originates from the epicardium, a multipotent epithelium that until now is only established to normally generate cardiac fibroblasts and coronary smooth muscle cells. We show that adoption of the adipocyte fate in vivo requires activation of the peroxisome proliferator activated receptor gamma (PPARγ) pathway, and that this fate can be ectopically induced in mouse ventricular epicardium, either in embryonic or adult stages, by expression and activation of PPARγ at times of epicardium–mesenchymal transformation. Human embryonic ventricular epicardial cells natively express PPARγ, which explains the abundant presence of fat seen in human hearts at birth and throughout life.

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Section: Discussionmentioning

confidence: 87%

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Yamaguchi

Cavallero

Patterson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

130

116

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“…Peroxisome proliferator-activated receptor g (PPARg) is a major regulator of adipogenesis and adipose tissue insulin sensitivity. 27 PPARg protein levels were reduced in chow diet-fed NOX4-deficient mice compared with WT mice. HFD feeding led to a decrease in PPARg expression in both WT and NOX4-deficient mice that diminished the difference between genotypes (P ¼ 0.013 Student's t-test) (Figure 3m).…”

Section: Resultsmentioning

confidence: 99%

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

Mouche

Sajic

et al. 2012

Int J Obes

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OBJECTIVE: NADPH oxidase 4 (NOX4) is a reactive oxygen species (ROS) producing NADPH oxidase that regulates redox homeostasis in diverse insulin-sensitive cell types. In particular, NOX4-derived ROS is a key modulator of adipocyte differentiation and mediates insulin receptor signaling in mature adipocytes in vitro. Our study was aimed at investigating the role of NOX4 in adipose tissue differentiation, whole body metabolic homeostasis and insulin sensitivity in vivo. DESIGN: Mice with genetic ablation of NOX4 (NOX4-deficient mice) were subjected to chow or high-fat-containing diet for 12 weeks. Body weight gain, adiposity, insulin sensitivity, and adipose tissue and liver gene and protein expression were analyzed and compared with similarly treated wild-type mice. RESULTS: Here, we report that NOX4-deficient mice display latent adipose tissue accumulation and are susceptible to diet-induced obesity and early onset insulin resistance. Obesity results from accelerated adipocyte differentiation and hypertrophy, and an increase in whole body energy efficiency. Insulin resistance is associated with increased adipose tissue hypoxia, inflammation and adipocyte apoptosis. In the liver, more severe diet-induced steatosis was observed due to the lack of proper upregulation of mitochondrial fatty acid b-oxidation. CONCLUSION: These findings identify NOX4 as a regulator of metabolic homeostasis. Moreover, they indicate an anti-adipogenic role for NOX4 in vivo and reveal its function as a protector against the development of diet-induced obesity, insulin resistance and hepatosteatosis.

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“…We found that the Pro12 allele of PPARG2 was significantly associated with elevated adipocyte IR index and nominally associated with increased liver IR. Peroxisome proliferator-activated receptor (PPAR)γ is a nuclear factor regulating transcriptor of various genes, particularly adiposespecific genes involved in adipocyte differentiation, and contributes to regulation of NEFA metabolism by stimulating uptake, storage and oxidation of NEFA in adipocytes [25]. The relevant SNP has been previously shown to be associated with insulin sensitivity [1,26,27].…”

Section: Discussionmentioning

confidence: 99%

Association of indices of liver and adipocyte insulin resistance with 19 confirmed susceptibility loci for type 2 diabetes in 6,733 non-diabetic Finnish men

et al. 2010

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Aims/hypothesis Of the confirmed type 2 diabetes susceptibility loci only a few are known to affect insulin sensitivity. We examined the association of indices of hepatic and adipocyte insulin resistance (IR) with 19 confirmed type 2 diabetes risk loci in a large population-based study. Methods Non-diabetic participants (n=8,460, age 57.3± 7.0 years, BMI 26.8±3.8 kg/m 2 ; mean ± SD) from a population-based cohort underwent an OGTT. Of them, 6,733 non-diabetic men were genotyped for single nucleotide polymorphisms (SNPs) in or near PPARG2 (also known as PPARG), KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, MTNR1B and SNP rs7480010. We investigated hepatic IR with a new index of liver IR. The adipocyte IR index was defined as a product of fasting NEFA and plasma insulin levels. Results Type 2 diabetes risk SNPs in or near KCNJ11 and HHEX were significantly (p<0.0013), and those in or near CDKN2B, NOTCH2 and MTNR1B were nominally (p<0.05), associated with decreased liver IR index. The Pro12 allele of PPARG2 was significantly associated with a high adipocyte IR index and nominally associated with high liver IR. Conclusions/interpretation The Pro12 allele of PPARG2 seems to impair insulin's antilipolytic effect, leading to high NEFA release in the fasting state and IR. In addition, the type 2 diabetes risk alleles of KCNJ11 and HHEX, which are known to impair insulin secretion, were associated with increased hepatic insulin sensitivity.

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Fat poetry: a kingdom for PPARγ

Cited by 135 publications

References 266 publications

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

Association of indices of liver and adipocyte insulin resistance with 19 confirmed susceptibility loci for type 2 diabetes in 6,733 non-diabetic Finnish men

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