Distinct Subsets of Hypothalamic Genes Are Modulated by Two Different Thermogenesis‐inducing Stimuli

Abstract

Obesity results from an imbalance between food intake and energy expenditure, two vital functions that are tightly controlled by specialized neurons of the hypothalamus. The complex mechanisms that integrate these two functions are only beginning to be deciphered. The objective of this study was to determine the effect of two thermogenesis-inducing conditions, i.e., ingestion of a high-fat (HF) diet and exposure to cold environment, on the expression of 1,176 genes in the hypothalamus of Wistar rats. Hypothalamic gene expression was evaluated using a cDNA macroarray approach. mRNA and protein expressions were determined by reverse-transcription PCR (RT-PCR) and immunoblot. Cold exposure led to an increased expression of 43 genes and to a reduced expression of four genes. HF diet promoted an increased expression of 90 genes and a reduced expression of 78 genes. Only two genes (N-methyl-d-aspartate (NMDA) receptor 2B and guanosine triphosphate (GTP)-binding protein G-alpha-i1) were similarly affected by both thermogenesis-inducing conditions, undergoing an increment of expression. RT-PCR and immunoblot evaluations confirmed the modulation of NMDA receptor 2B and GTP-binding protein G-alpha-i1, only. This corresponds to 0.93% of all the responsive genes and 0.17% of the analyzed genes. These results indicate that distinct environmental thermogenic stimuli can modulate predominantly distinct profiles of genes reinforcing the complexity and multiplicity of the hypothalamic mechanisms that regulate energy conservation and expenditure.

Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet

“…In fact, a low-protein diet was reported to result in reduced activation of satiety centers, leading to increased food intake (Du et al 2000). In the offspring of dams submitted to a protein-restricted diet, during gestation and lactation, hyperphagia associated with an increased expression of NPY and AgRP in the hypothalamus was described (De Souza et al 2008;Orozco-Solis Fig. 3 Food intake profile and hypothalamic STAT3 activation in response to leptin in mice that underwent protein-restriction with or without HFD and Tau supplementation.…”

Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis

“…It is tempting to speculate that the interaction between ASP and MSG may converge at the level of the NMDA receptor for which glutamate and aspartate are both ligands; however the situation is likely to be far more intricate. Glutamate is the most abundant excitatory neurotransmitter and plays a pivotal role in the formation of synapses, integration of convergent signals, the establishment of N-methyl-D-aspartate (NMDA) receptor-dependent long term potentiation, and several critical autonomic functions including appetite regulation and thermogenesis [55]. However, elevated levels of glutamate have been shown to cause selective neuronal damage in the brains of infant mice, in particular the highly vascularized areas located outside the blood–brain barrier such as the median eminence and the hypothalamic arcuate nucleus [56,57].…”

Diet-Induced Inflammation of the Hypothalamus in Obesity

“…Among these, a number of cytokines were identified. Real-time PCR, ELISA and immunoblot demonstrated that expressions of tumor necrosis factor (TNF)-␣ , interleukin-1 ␤ and interleukin-6 were significantly increased in the hypothalamus of rats fed on a high-fat diet [16,22] .…”

“…Interestingly, analyzing the genes modulated by functional clustering revealed that the majority of the genes undergoing differential expression belong to families of genes with immunological function [22] . Among these, a number of cytokines were identified.…”

“…Long-term feeding on a fat-rich diet modulates the expression of more than 10% of genes expressed in the hypothalamus of rodents [8,22] . Interestingly, analyzing the genes modulated by functional clustering revealed that the majority of the genes undergoing differential expression belong to families of genes with immunological function [22] .…”