Nutritional regulation of genome-wide association obesity genes in a tissue-dependent manner

• Main Authors: Yoganathan Piriya, Karunakaran Subashini, Ho Maggie M, Clee Susanne M
• Format: Article
• Language: English
• Published: BMC 2012-07-01
• Series: Nutrition & Metabolism
• Subjects: Obesity genes; Genome-wide association; Gene expression; High fat diet; Feeding and fasting; Gene-diet interaction; Adipose tissue; Brain
• Online Access: http://www.nutritionandmetabolism.com/content/9/1/65

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) have recently identified several new genetic variants associated with obesity. The majority of the variants are within introns or between genes, suggesting they affect gene expression, although it is not clear which of the nearby genes they affect. Understanding the regulation of these genes will be key to determining the role of these variants in the development of obesity and will provide support for a role of these genes in the development of obesity.</p> <p>Methods</p> <p>We examined the expression of 19 GWAS obesity genes in the brain and specifically the hypothalamus, adipose tissue and liver of mice by real-time quantitative PCR. To determine whether these genes are nutritionally regulated, as may be expected for genes affecting obesity, we compared tissues from fasting and non-fasting animals and tissues from mice consuming a high fat high sucrose diet in comparison to standard rodent chow.</p> <p>Results</p> <p>We found complex, tissue-dependent patterns of nutritional regulation of most of these genes. For example, <it>Bat2</it> expression was increased ~10-fold in the brain of fed mice but was lower or unchanged in the hypothalamus and adipose tissue. <it>Kctd15</it> expression was upregulated in the hypothalamus, brain and adipose tissue of fed mice and downregulated by high fat feeding in liver, adipose tissue and the hypothalamus but not the remainder of the brain. <it>Sh2b1</it> expression in the brain and <it>Faim2</it> expression in adipose tissue were specifically increased >20-fold in fed mice. <it>Tmem18</it> expression in adipose tissue but not the brain was reduced 80% by high fat feeding. Few changes in the expression of these genes were observed in liver.</p> <p>Conclusions</p> <p>These data show nutritional regulation of nearly all these GWAS obesity genes, particularly in the brain and adipose tissue, and provide support for their role in the development of obesity. The complex patterns of nutritional and tissue-dependent regulation also highlight the difficulty that may be encountered in determining how the GWAS genetic variants affect gene expression and consequent obesity risk in humans where access to tissues is constrained.</p>