Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes[S]

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Abstract

Peroxisome proliferator-activated receptor-α (PPARα) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPARα activation affects energy metabolism in white adipose tissue (WAT). Activation of PPARα by its agonist (bezafibrate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specific PPARα agonist, during adipocyte differentiation enhanced glycerol-3-phosphate dehydrogenase activity, insulin-stimulated glucose uptake, and adipogenic gene expression. However, triglyceride accumulation was not increased by PPARα activation. PPARα activation induced expression of target genes involved in FA oxidation and stimulated FA oxidation. In WAT of KK mice treated with bezafibrate, both adipogenic and FA oxidation-related genes were significantly upregulated. These changes in mRNA expression were not observed in PPARα-deficient mice. Bezafibrate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPARα was recruited to promoter regions of both adipogenic and FA oxidation-related genes in the presence of GW7647 in 3T3-L1 adipocytes. These findings indicate that the activation of PPARα affects energy metabolism in adipocytes, and PPARα activation in WAT may contribute to the clinical effects of fibrate drugs.

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Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.

Ali Mokdad, Earl S. Ford, Barbara BOWMAN … (2003)

Obesity and diabetes are increasing in the United States. To estimate the prevalence of obesity and diabetes among US adults in 2001. Random-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001. Body mass index, based on self-reported weight and height and self-reported diabetes. In 2001 the prevalence of obesity (BMI > or =30) was 20.9% vs 19.8% in 2000, an increase of 5.6%. The prevalence of diabetes increased to 7.9% vs 7.3% in 2000, an increase of 8.2%. The prevalence of BMI of 40 or higher in 2001 was 2.3%. Overweight and obesity were significantly associated with diabetes, high blood pressure, high cholesterol, asthma, arthritis, and poor health status. Compared with adults with normal weight, adults with a BMI of 40 or higher had an odds ratio (OR) of 7.37 (95% confidence interval [CI], 6.39-8.50) for diagnosed diabetes, 6.38 (95% CI, 5.67-7.17) for high blood pressure, 1.88 (95% CI,1.67-2.13) for high cholesterol levels, 2.72 (95% CI, 2.38-3.12) for asthma, 4.41 (95% CI, 3.91-4.97) for arthritis, and 4.19 (95% CI, 3.68-4.76) for fair or poor health. Increases in obesity and diabetes among US adults continue in both sexes, all ages, all races, all educational levels, and all smoking levels. Obesity is strongly associated with several major health risk factors.

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Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.

S Kersten, J Seydoux, J M Peters … (1999)

Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPARalpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARalpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPARalpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARalpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARalpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPARalpha mRNA is induced during fasting in wild-type mice. The data indicate that PPARalpha plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.

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The epidemiology of obesity.

Cynthia L Ogden, Susan Z Yanovski, Margaret D Carroll … (2007)

In the United States, obesity among adults and overweight among children and adolescents have increased markedly since 1980. Among adults, obesity is defined as a body mass index of 30 or greater. Among children and adolescents, overweight is defined as a body mass index for age at or above the 95th percentile of a specified reference population. In 2003-2004, 32.9% of adults 20-74 years old were obese and more than 17% of teenagers (age, 12-19 y) were overweight. Obesity varies by age and sex, and by race-ethnic group among adult women. A higher body weight is associated with an increased incidence of a number of conditions, including diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease, and with an increased risk of disability. Obesity is associated with a modestly increased risk of all-cause mortality. However, the net effect of overweight and obesity on morbidity and mortality is difficult to quantify. It is likely that a gene-environment interaction, in which genetically susceptible individuals respond to an environment with increased availability of palatable energy-dense foods and reduced opportunities for energy expenditure, contributes to the current high prevalence of obesity. Evidence suggests that even without reaching an ideal weight, a moderate amount of weight loss can be beneficial in terms of reducing levels of some risk factors, such as blood pressure. Many studies of dietary and behavioral treatments, however, have shown that maintenance of weight loss is difficult. The social and economic costs of obesity and of attempts to prevent or to treat obesity are high.

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Author and article information

Journal

Journal ID (nlm-ta): J Lipid Res

Journal ID (iso-abbrev): J. Lipid Res

Journal ID (publisher-id): jlr

Title: Journal of Lipid Research

Publisher: The American Society for Biochemistry and Molecular Biology

ISSN (Print): 0022-2275

ISSN (Electronic): 1539-7262

Publication date (Print and electronic): May 2011

Publication date (Print): May 2011

Publication date PMC-release: May 2011

Volume: 52

Issue: 5

Pages: 873-884

Affiliations

[* ]Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University , Uji, Kyoto, Japan

[† ]Department of Food Science and Nutrition, Nara Women's University , Nara, Japan

Author notes

[1 ]To whom correspondence should be addressed. e-mail: fat@ 123456kais.kyoto-u.ac.jp

Article

Publisher ID: m011320

DOI: 10.1194/jlr.M011320

PMC ID: 3073464

PubMed ID: 21324916

SO-VID: c83f6d34-5e22-4aa5-ad87-0e32045e260a

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Creative Commons Attribution Non-Commercial License applies to Author Choice Articles

History

Date received : 16 September 2010

Date revision received : 1 February 2011

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Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes[S]

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Karger: Nutrition and Dietetics

Most cited references 42

Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.

Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.

The epidemiology of obesity.

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Cited by 68

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