Unconventional microarray design reveals the response to obesity is largely tissue specific: analysis of common and divergent responses to diet-induced obesity in insulin-sensitive tissues

Abstract

Obesity is a chronic condition involving the excessive accumulation of adipose tissue that adversely affects all systems in the body. The aim of the present study was to employ an unbiased, genome-wide assessment of transcript abundance in order to identify common gene expression pathways within insulin-sensitive tissues in response to dietary-induced diabetes. Following 20 weeks of chow or high-fat feeding (60% kcal), age-matched mice underwent a euglycemic-hyperinsulinemic clamp to assess insulin sensitivity. High-fat-fed animals were obese and highly insulin resistant, disposing of ∼75% less glucose compared with their chow-fed counterparts. Tissues were collected, and gene expression was examined by microarray in 4 tissues known to exhibit obesity-related metabolic disturbances: white adipose tissue, skeletal muscle, liver, and heart. A total of 463 genes were differentially expressed between diets. Analysis of individual tissues showed skeletal muscle to exhibit the largest number of differentially expressed genes (191) in response to high-fat feeding, followed by adipose tissue (169), liver (115), and heart (65). Analyses revealed that the response of individual genes to obesity is distinct and largely tissue specific, with less than 10% of transcripts being shared among tissues. Although transcripts are largely tissue specific, a systems approach shows numerous commonly activated pathways, including those involved in signal transduction, inflammation, oxidative stress, substrate transport, and metabolism. This suggests a coordinated attempt by tissues to limit metabolic perturbations occurring in early-stage obesity. Many identified genes were associated with a variety of disorders, thereby serving as potential links between obesity and its related health risks.

Prediabetic changes in gene expression induced by aspartame and monosodium glutamate in Trans fat-fed C57Bl/6 J mice

“…Others have also shown higher numbers of adipose tissue differentially expressed genes (DEGs) compared to liver, both in response to fasting [42], and during LPS-induced inflammation [43]. Most recently, high-fat feeding has been shown to induce obesogenic gene expression changes in 4 murine tissues, with adipose tissue producing the second highest number of DEGs in the following order: skeletal muscle > adipose > liver > heart [44]. …”

“…Previous studies have shown that transcription of hepatic Acc2 is markedly upregulated by increased food intake [45], insulin, and dexamethasone [46]. Unlike Acc1 which stimulates lipogenesis, Acc2 is known to inhibit lipolysis; and its structure has an N-terminal extension containing a mitochondrial-targeting motif which allows Acc2 to associate with Cpt1 on the outer mitochondrial membrane, thus regulating ß-oxidation at an early stage in the process [44]. High-fat diets and obesity have previously been associated with decreased expression of Ppargc1a, the dominant regulator of oxidative metabolism [41]; and whereas we have previously shown that Ppargc1a expression is reduced by intake of TFA compared to low-fat controls [9], we now demonstrate that levels of this transcription factor can be further attenuated by ASP + MSG exposure, both in the liver and particularly in the visceral adipose tissue.…”

Tissue Specific Impacts of a Ketogenic Diet on Mitochondrial Dynamics in the BTBRT+tf/j Mouse

“…Samples were run in triplicate on the same reaction plate using the CFX96 Real-Time PCR Detection System (Bio-Rad) with β-actin as a loading control. Data analysis was performed in accordance with previously published work using the 2 −ΔΔCt method (Lee et al, 2012). …”

Functional Genomics of Cardioprotection by Ischemic Conditioning and the Influence of Comorbid Conditions: Implications in Target Identification

“…Several of these genes have not been implicated in cardiovascular diseases before. Tissue specific gene expression changes were also compared in obese animals [29]. In high-fat chow fed mice expression of several hundred genes is altered, although only a fraction of them is common between tissues.…”