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Exploring Food-induced Obesity and Macrophage Related Differential Genes in Subcutaneous and Visceral Fat between Obese and Normal Individuals

ABSTRACT: As a serious public health problem nowadays, obesity and its complications are receiving gradually more attention, especially on how food-induced obesity causes the expansion of adipose tissue and leads to the occurrence of metabolic inflammation and infiltration of immune cells. It's still worth mentioning that numerous genes in adipose tissue which differ between obese and normal individuals in food-induced obesity were not insufficiently studied. Applying machine learning methods and natural language processing methods on transcriptome datasets and PubMed abstracts, we investigated 8 genes with differential expression and high association with macrophages in the visceral and subcutaneous adipose tissue between obese and normal individuals, and meanwhile low correlation with leptin. Compared with normal group, Quantitative Real-time Polymerase Chain Reaction, Western Blot, immunohistochemistry, immunofluorescence and other subsequent animal experiments on the 8 filtered genes were applied in the adipose tissue of C57BL/6J and OB/OB mice, we found that the expression of glycoprotein IX (GP9), MHC class I polypeptide related sequence B (MICB), CDGSH iron sulfur domain 1 (CISD1) and Pre-mRNA-processing factor 19 (PRPF19) in protein level were down-regulated in visceral fat of obese mice induced by high-fat diet. And these obese mice showed decreased levels of mannosidase alpha class 2B member 1 (MAN2B1) and TYRO protein tyrosine kinase binding protein (TYROBP) in their subcutaneous adipose tissue, while phosphate and tension homology deleted on chromosome pten (PTEN) and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) had been sufficiently studied. The pattern in OB/OB mouse was dramatically different with these patterns. Through double immunofluorescence staining, it was found that all genes were co-localized with CD206, which was the marker of M1 and M2 macrophage in adipose tissue. Further interacting drugs for the genes were calculated and subsequently circumin and beta-catonin were proved to be interacting with these genes and functioned in inhibiting food-induced obesity. Further knowledge gragh was constructed to illustrate the relationship between obesity, filtered genes, drugs and related concepts. To summarize our findings, we discovered some new differential genes in adipose tissue which could potentially establish a new connection between adipose tissue macrophages and food-induced obesity. Furthermore, they offered unique insights into exploring the mechanism of adipose tissue genes related to food-induced obesity and related diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE243559 | GEO | 2023/09/28

REPOSITORIES: GEO

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Project description:The expression of adipogenic genes is decreased in obesity and diabetes mellitus ; Samuel T. Nadler*, Jonathan P. Stoehr*, Kathryn L. Schueler*, Gene Tanimoto, Brian S. Yandell, and Alan D. Attie*,Â§ ; Departments of * Biochemistry, and Statistics and Horticulture, University of Wisconsin, Madison, WI, 53706; and Affymetrix, Inc., Santa Clara, CA 95051 ; Communicated by Neal L. First, University of Wisconsin, Madison, WI, July 13, 2000 (received for review April 3, 2000) ; Obesity is strongly correlated with type 2 diabetes mellitus, a common disorder of glucose and lipid metabolism. Although adipocytes are critical in obesity, their role in diabetes has only recently been appreciated. We conducted studies by using DNA microarrays to identify differences in gene expression in adipose tissue from lean, obese, and obese-diabetic mice. The expression level of over 11,000 transcripts was analyzed, and 214 transcripts showed significant differences between lean and obese mice. Surprisingly, the expression of genes normally associated with adipocyte differentiation were down-regulated in obesity. Not all obese individuals will become diabetic; many remain normoglycemic despite profound obesity. Understanding the transition to obesity with concomitant diabetes will provide important clues to the pathogenesis of type 2 diabetes. Therefore, we examined the levels of gene expression in adipose tissue from five groups of obese mice with varying degrees of hyperglycemia, and we identified 88 genes whose expression strongly correlated with diabetes severity. This group included many genes that are known to be involved in signal transduction and energy metabolism as well as genes not previously examined in the context of diabetes. Our data show that a decrease in expression of genes normally involved in adipogenesis is associated with obesity, and we further identify genes important for subsequent development of type 2 diabetes mellitus. Experiment Overall Design: For obesity study, lean samples include C57BL/6J lean, (C57BL/6J X BTBR) F1 and BTBR lean, obese sampples incluse C57BL/6J-ob/ob, (C57BL/6J X BTBR) F2-ob/ob and BTBR-ob/ob. All samples are subjected to Mu11K A and B arrays. Experiment Overall Design: For diabetes study, B6-ob/ob, (C57BL/6J X BTBR) F2-ob/ob low glucose, (C57BL/6J X BTBR) F2-ob/ob medium glucose, (C57BL/6J X BTBR) F2-ob/ob high glucose, and BTBR-ob/ob samples were analyzed for genes whose expression levels changes correlated with the plasma glucose levels in these mice. All samples are subjected to Mu11K A and B arrays.

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Exploring Food-induced Obesity and Macrophage Related Differential Genes in Subcutaneous and Visceral Fat between Obese and Normal Individuals

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