Regulation of PPAR gamma gene expression by nutrition and obesity in rodents.

Abstract

The orphan nuclear receptor, peroxisome proliferator-activated receptor (PPAR) ␥ , is implicated in mediating expression of fat-specific genes and in activating the program of adipocyte differentiation. The potential for regulation of PPAR ␥ gene expression in vivo is unknown. We cloned a partial mouse PPAR ␥ cDNA and developed an RNase protection assay that permits simultaneous quantitation of mRNAs for both ␥ 1 and ␥ 2 isoforms encoded by the PPAR ␥ gene. Probes for detection of adipocyte P2, the obese gene product, leptin, and 18S mRNAs were also employed. Both ␥ 1 and ␥ 2 mRNAs were abundantly expressed in adipose tissue. PPAR ␥ 1 expression was also detected at lower levels in liver, spleen, and heart; whereas, ␥ 1 and ␥ 2 mRNA were expressed at low levels in skeletal muscle. Adipose tissue levels of ␥ 1 and ␥ 2 were not altered in two murine models of obesity (gold thioglucose and ob/ob), but were modestly increased in mice with toxigene-induced brown fat ablation uncoupling protein diphtheria toxin A mice. Fasting (12-48 h) was associated with an 80% fall in PPAR ␥ 2 and a 50% fall in PPAR ␥ 1 mRNA levels in adipose tissue. Western blot analysis demonstrated a marked effect of fasting to reduce PPAR ␥ protein levels in adipose tissue. Similar effects of fasting on PPAR ␥ mRNAs were noted in all three models of obesity. Insulin-deficient (streptozotocin) diabetes suppressed adipose tissue ␥ 1 and ␥ 2 expression by 75% in normal mice with partial restoration during insulin treatment. Levels of adipose tissue PPAR ␥ 2 mRNA were increased by 50% in normal mice exposed to a high fat diet. In obese uncoupling protein diphtheria toxin A mice, high fat feeding resulted in de novo induction of PPAR ␥ 2 expression in liver. We conclude (

PPARs and adipocyte function

“…Accordingly, its expression is highest post-prandially and is down-regulated by fasting consistent with the stimulatory effect of insulin on PPAR expression [42,43]. In the context of a high-fat diet, docking protein 1 (DOK1)-mediated insulin signalling also enhances PPAR activity by counteracting the inhibitory effect of extra-cellular signal-regulated kinase (ERK)-mediated PPAR phosphorylation (thereby promoting adipocyte hypertrophy).…”

Time-Dependent Effects of a High-Energy-Yielding Diet on the Regulation of Specific White Adipose Tissue Genes

“…The management of excess fat deposition has been fraught with disappointment, in part, because the mechanisms regulating fuel homeostasis and adiposity are incompletely understood (2). In this context, several studies have been designed to investigate the effects of macronutrients or the nutritional status on gene expression in white adipose tissue (WAT), as the major energy storing tissue as well as in other tissues (3)(4)(5).…”

The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

“…The PPAR family (α, β/δ and γ) integrates energy regulation with lipid and glucose metabolism and affects insulin sensitivity (Kota et al, 2005). Furthermore, PPARγ expression in the adipose tissue is nutritionally regulated (Vidal-Puig et al, 1996).…”