PPAR‐α agonist elicits metabolically active brown adipocytes and weight loss in diet‐induced obese mice

Abstract

Obesity is considered a public health problem worldwide. Fenofibrate, a selective peroxisome proliferator-activated receptor α (PPAR-α) agonist, elicits weight loss in animal models. This study aimed to examine the effects of fenofibrate on energy expenditure, body mass (BM) and gene expression of thermogenic factors in brown adipose tissue of diet-induced obese mice. Male C57BL/6 mice were fed a standard chow (SC; 10% lipids) diet or a high-fat (HF; 50% lipids) diet for 10 weeks. Afterwards, groups were subdivided as SC, SC-F, HF and HF-F (n = 10, each). Treatment with fenofibrate (100 mg kg(-1) BM mixed into the diet) lasted 5 weeks. Treated groups had reduced final BM compared with their counterparts (p < 0·05), explained by the increase in energy expenditure, CO2 production and O2 consumption after treatment with fenofibrate (p < 0·05). Similarly, genes involved in thermogenesis as PPAR-α, PPAR-γ coactivator 1α, nuclear respiratory factor 1, mitochondrial transcription factor A (Tfam), PR domain containing 16 (PRDM16), β-3 adrenergic receptor (β3-AR), bone morphogenetic protein 8B and uncoupling protein 1 were significantly expressed in brown adipocytes after the treatment (p < 0·05). All observations ensure that selective PPAR-α agonist can induce thermogenesis by increasing energy expenditure and enhancing the expression of genes involved in the thermogenic pathway. These results suggest fenofibrate as a coadjutant drug for the treatment of obesity.

Fenofibrate, but not ezetimibe, prevents fatty liver disease in mice lacking phosphatidylethanolamine N-methyltransferase

“…3 ). Consistent with previous reports (23, 24), treatment of Pemt +/+ mice with fenofibrate prevented diet-induced obesity (Fig. 3A).…”

Shared PPARα/γ Target Genes Regulate Brown Adipocyte Thermogenic Function

“…TZD PPARg agonists like rosiglitazone (rosi) are well known to increase brown adipocyte activity and induce beige adipocyte formation (Kelly et al, 1998;Ohno et al, 2012). It is also clear that PPARa agonists like fenofibrate (feno) similarly increase thermogenic gene expression in brown and beige fat (Rachid et al, 2015).…”

Effects of ramelteon on cardiac injury and adipose tissue pathology in rats with metabolic syndrome

“…A reduction in the number of capillaries surrounding brown adipocytes results in mitochondrial hypoxia and thereby leads to increased ROS production and whitening of BAT. Impairment of the thermogenic function of BAT in MetS accelerates body weight gain . In the present study, a ramelteon‐induced improvement in heat production and energy release by BAT may have contributed to the associated amelioration of weight gain in DS/obese rats.…”