Meta-Review of Protein Network Regulating Obesity Between Validated Obesity Candidate Genes in the White Adipose Tissue of High-Fat Diet-Induced Obese C57BL/6J Mice

Abstract

Worldwide obesity and related comorbidities are increasing, but identifying new therapeutic targets remains a challenge. A plethora of microarray studies in diet-induced obesity models has provided large datasets of obesity associated genes. In this review, we describe an approach to examine the underlying molecular network regulating obesity, and we discuss interactions between obesity candidate genes. We conducted network analysis on functional protein-protein interactions associated with 25 obesity candidate genes identified in a literature-driven approach based on published microarray studies of diet-induced obesity. The obesity candidate genes were closely associated with lipid metabolism and inflammation. Peroxisome proliferator activated receptor gamma (Pparg) appeared to be a core obesity gene, and obesity candidate genes were highly interconnected, suggesting a coordinately regulated molecular network in adipose tissue. In conclusion, the current network analysis approach may help elucidate the underlying molecular network regulating obesity and identify anti-obesity targets for therapeutic intervention.

Flavonoid-rich Chardonnay grape seed flour supplementation ameliorates diet-induced visceral adiposity, insulin resistance, and glucose intolerance via altered adipose tissue gene expression

“…The present study showed that flavonoid-rich ChrSd supplementation significantly down-regulated the expression of genes related to oxidative stress, innate immune and inflammatory responses; i.e., regulation of nitric-oxide synthase activity (Nostrin and Nos2). In addition, ChrSd supplementation downregulated the expression of genes encoding adipogenic factors such as Gdf3 (Andersson, Korach-Andre, Reissmann, Ibanez, & Bertolino, 2008), Gpd1, Cebpb, Lep (Kim et al, 2014), Tgfb1, Tgfbr1 (Yadav et al, 2011), and Lmna (Lelliott et al, 2002), and genes involved in fatty acid synthesis (Elovl1), while it up-regulated genes for fatty acid β-oxidation (Ppara and Echdc2), leading to reduced HF-induced obesity. This alteration in adipose tissue was accompanied by a significantly lower total body weight and improved HF-induced insulin resistance and glucose intolerance, as compared to the control group.…”

Time-course microarrays reveal modulation of developmental, lipid metabolism and immune gene networks in intrascapular brown adipose tissue during the development of diet-induced obesity

“…Network analysis was conducted using the Ingenuity Knowledge base, which is a large repository of biological interactions between proteins, RNAs, genes, isoforms, metabolites, complexes, cells, tissues, drugs and diseases, manually curated by experts based on over 3.58 million published studies. 20 The Ingenuity Knowledge base, includes biological interaction data on 19 600 human and 14 700 mouse genes. For each time-point, molecular networks were constructed of direct physical, transcriptional and enzymatic interactions.…”

Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation

“…A recent paper describing a meta-review of micro-array data on high-fat DIO in C57BL/6J mice found that upregulated genes were associated with fatty acid synthesis, inflammation, signal transduction and transporters, and energy homeostasis [ 22 ]. Down-regulated genes were associated with sterol biosynthesis, insulin sensitivity and oxidative stress.…”