Expression of Peroxisome Proliferator-Activated Receptor-γ in Key Neuronal Subsets Regulating Glucose Metabolism and Energy Homeostasis

Abstract

In addition to increasing insulin sensitivity and adipogenesis, peroxisome proliferator-activated receptor (PPAR)-gamma agonists cause weight gain and hyperphagia. Given the central role of the brain in the control of energy homeostasis, we sought to determine whether PPARgamma is expressed in key brain areas involved in metabolic regulation. Using immunohistochemistry, PPARgamma distribution and its colocalization with neuron-specific protein markers were investigated in rat and mouse brain sections spanning the hypothalamus, the ventral tegmental area, and the nucleus tractus solitarius. In several brain areas, nuclear PPARgamma immunoreactivity was detected in cells that costained for neuronal nuclei, a neuronal marker. In the hypothalamus, PPARgamma immunoreactivity was observed in a majority of neurons in the arcuate (including both agouti related protein and alpha-MSH containing cells) and ventromedial hypothalamic nuclei and was also present in the hypothalamic paraventricular nucleus, the lateral hypothalamic area, and tyrosine hydroxylase-containing neurons in the ventral tegmental area but was not expressed in the nucleus tractus solitarius. To validate and extend these histochemical findings, we generated mice with neuron-specific PPARgamma deletion using nestin cre-LoxP technology. Compared with littermate controls, neuron-specific PPARgamma knockout mice exhibited dramatic reductions of both hypothalamic PPARgamma mRNA levels and PPARgamma immunoreactivity but showed no differences in food intake or body weight over a 4-wk study period. We conclude that: 1) PPARgamma mRNA and protein are expressed in the hypothalamus, 2) neurons are the predominant source of PPARgamma in the central nervous system, although it is likely expressed by nonneuronal cell types as well, and 3) arcuate nucleus neurons that control energy homeostasis and glucose metabolism are among those in which PPARgamma is expressed.

Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation

“…Similarly, the glial cell markers S100 and GFAP are expressed in a great variety of normal and pathological tissues [50,51]. On the other hand, neural cells can express mesodermal-specific markers such as the osteogenic markers osteopontin and osteocalcin and the adipogenic marker PPAR [52,53].…”

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

“…The expression of PPAR isoforms has been detected in mouse, ovine and human pituitary gland [13,14] and in rodent hypothalamus [15], but their significance in the regulation of reproductive functions at the level of hypothalamic-pituitary (HP) remains poorly understood. It has been demonstrated that PPARg activation by TZDs inhibited the development of pituitary adenomas in mice and humans [18,19] but did not affect the secretion of prolactin (PRL), follicle-stimulating hormone (FSH) or luteinizing hormone (LH) by ovine pituitary or LH by murine LbetaT2 gonadotrophic pituitary tumor cell line [16].…”

Neuroprotection by dietary restriction and the PPAR transcription complex

“…The second PPAR discovered in mammals, as homologous to PPAR-alpha, was PPARgamma [64,65] PPAR-gamma exhibits an expression pattern broadly similar to PPARalpha, including, notably, low but detectable expression in the brain [64], including in neurons [66]. Like PPAR-alpha, PPAR-gamma is activated by a variety of lipophilic substances Compared with the neuroprotective effects of PPAR-alpha agonists described above, neuroprotective effects of PPAR-gamma agonists have been far more robustly reported, and have been the subject of several recent reviews [68,69].…”