Transcriptional profiling of hypothalamus during development of adiposity in genetically selected fat and lean chickens

Abstract

The hypothalamus integrates peripheral signals to regulate food intake, energy metabolism, and ultimately growth rate and body composition in vertebrates. Deviations in hypothalamic regulatory controls can lead to accumulation of excess body fat. Many regulatory genes involved in this process remain unidentified, and comparative studies may be helpful to unravel evolutionarily conserved mechanisms controlling body weight and food intake. In the present study, divergently selected fat (FL) and lean (LL) lines of chickens were used to characterize differences in hypothalamic gene expression in these unique genetic lines that develop differences in adiposity without differences in food intake or body weight. Hypothalamic transcriptional profiles were defined with cDNA microarrays before and during divergence of adiposity between the two lines. Six differentially expressed genes identified in chickens are related to genes associated with control of body fat in transgenic or knockout mice, supporting the importance of these genes across species. We identified differences in expression of nine genes involved in glucose metabolism, suggesting that alterations in hypothalamic glycolysis might contribute to differences in levels of body fat between genotypes. Expression of the sweet taste receptor (TAS1R1), which in mammals is involved in glucose sensing and energy uptake, was also higher in FL chickens, suggesting that early differences in glucose sensing might alter the set point for subsequent body composition. Differences in expression of genes associated with tumor necrosis factor (TNF) signaling were also noted. In summary, we identified alterations in transcriptional and metabolic processes within the hypothalamus that could contribute to excessive accumulation of body fat in FL chickens in the absence of differences in food intake, thereby contributing to the genetic basis for obesity in this avian model.

Transcriptional analysis of abdominal fat in genetically fat and lean chickens reveals adipokines, lipogenic genes and a link between hemostasis and leanness

“…Furthermore, the LEP gene is absent from the genome of all birds sequenced so far (i.e., chicken, turkey, zebra finch, budgerigar and duck). However, the leptin receptor ( LEPR ) gene is expressed in several chicken tissues [75-79]; and chicken LEPR is capable of activating the JAK-STAT pathway in vitro [80,81]. Similarly, components of TNF signaling are up regulated in the hypothalamus of LL chickens [79], although TNFA is yet to be identified in chickens .…”

“…However, the leptin receptor ( LEPR ) gene is expressed in several chicken tissues [75-79]; and chicken LEPR is capable of activating the JAK-STAT pathway in vitro [80,81]. Similarly, components of TNF signaling are up regulated in the hypothalamus of LL chickens [79], although TNFA is yet to be identified in chickens . Despite the absence of several mammalian adipokines (i.e., LEP, TNFA, RETN, PAI-1 , APOE , and ITLN1 ) and metabolic enzymes (i.e., LIPE ), adipogenesis and lipid metabolism in the chicken are robustly regulated by mechanisms that are, for the most part, similar to those described in mammals.…”

“…The up-regulation of TXNIP in abdominal fat of the FL during the period of maximal fatness (3–11 wk) could contribute to their enhanced lipogenesis and adiposity. Likewise, we have discovered another putative sensor of glucose, the sweet taste receptor 1 ( TAS1R1 ) gene, which is differentially expressed in the hypothalamus [79] and abdominal fat (Figure 2) of FL and LL chickens. Our observation of higher expression of TAS1R1 in the hypothalamus of the FL and abdominal fat of the LL suggest tissue specific regulation of this important tissue glucose sensor [124-126].…”

Chicken lines divergent for low or high abdominal fat deposition: a relevant model to study the regulation of energy metabolism

“…These differences between lines might at the hypothalamic level explain the greater ability of FL for body fat deposition. Byerly et al (2010) defined hypothalamic transcription profiles with cDNA microarrays before and during divergence between FL and LL chickens on adiposity. They found differential expression between lines of genes involved in the control of body fat, glucose metabolism, glucose sensing and TNF signalling.…”

Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees

“…The hypothalamic transcriptome and proteome of the Huoyan goose [54, 263] and the hypothalamic transcriptome of Sichuan white goose [125] have been profiled before, during, or after their egg laying periods in the interests of finding clues to improve the reproductive performance of these economically valuable domestic animals (also see Figure 1 of [254). In the interests of optimizing feed intake in chickens or to understand how they cope with environmentally-induced pressures, many studies have also examined the role of body composition, fasting, diet, or heat stress on gene expression in chicken hypothalamus (e.g., [51, 106, 416, 439]; see also [232]). Despite the intensive investigations of chicken hypothalamus for molecular mining and extraction, these studies have not contextualized sub-regional changes in expression for molecules in relation to published stereotaxic atlases of the chicken that include illustrations, maps and drawings of the hypothalamus with stereotaxic coordinates [112, 444, 471].…”