Elsevier

Metabolism

Volume 53, Issue 10, October 2004, Pages 1284-1289
Metabolism

Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice

https://doi.org/10.1016/j.metabol.2004.05.003Get rights and content

Abstract

Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor α (PPARα) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARα target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARα target genes encoding peroxisomal enzymes involved in fatty acid β-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARα activation, but not to differences in leptin production, between female OVX and Sham mice.

Section snippets

Animal treatments

For all experiments, 8-week-old mice (C57BL/6J) were housed and bred at the Korea Research Institute of Bioscience and Biotechnology under pathogen-free conditions with a standard 12-hour light/dark cycle. Prior to the administration of special diets, mice were fed standard rodent chow and water ad libitum. Female Sham and OVX mice were each randomly divided into 3 groups (n = 5 per group), which showed the uniformity in response to each treatment in the pilot study. The mice received a low-fat

Effects of fenofibrate on body weight gain and WAT mass in female mice

To determine whether fenofibrate reduces body weight gain and adiposity in female mice, the influence of fenofibrate treatment on body weight and WAT mass was examined in diet-induced obese female Sham and OVX C57BL/6J mice. Compared to their respective low-fat diet controls, the administration of a high-fat diet for 13 weeks increased body weight by 15.7% ± 0.7% in OVX mice and by 8.4% ± 0.5% in Sham mice, as shown in Fig 1. In contrast, compared to their respective high-fat diet-fed groups,

Discussion

This study was undertaken to verify whether fenofibrate prevents body weight gain and adiposity in female OVX and Sham C57BL/6J mice on a high-fat diet, and to determine whether PPARα is associated with these events.

Our results demonstrate that fenofibrate reduces body weight gain and WAT mass in high-fat diet-fed OVX mice, but fails to do so in Sham mice. Body weights of OVX mice were found to be higher than those of Sham mice 6 weeks after commencing the high-fat diet. Compared to high-fat

References (33)

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    The inhibitory effects of DF on obesity were comparable to those of the PPARα agonist fenofibrate. It was shown that PPARα activators reduced body weight gain and adipose tissue mass, at least in part, due to the increase of fatty acid oxidation (Jeong et al., 2004; Jeong and Yoon, 2009). Hypertrophied adipocytes secrete TNFα, leptin, free fatty acids, and high levels of inflammatory cytokines such as MCP-1, which are closely associated with metabolic syndromes including insulin resistance, type 2 diabetes, NAFLD, and cardiovascular disease (Xu et al., 2003; Curat et al., 2004; Despres and Lemieux, 2006; Jeong and Yoon, 2009).

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Supported by a Grant No. KRF-2003-015-C00621 from Korea Research Foundation.

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