Department of Biological Sciences, College of Arts and Sciences, University of Delaware, Newark, Delaware, United States.
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Physiol Genomics. 2024 Dec 1;56(12):819-832. doi: 10.1152/physiolgenomics.00080.2024. Epub 2024 Sep 30.
The accumulation of visceral adipose tissue (VAT) is strongly associated with cardiovascular disease and diabetes. In contrast, individuals with increased subcutaneous adipose tissue (SAT) without corresponding increases in VAT are associated with a metabolic healthy obese phenotype. These observations implicate dysfunctional VAT as a driver of disease processes, warranting investigation into obesity-induced alterations of distinct adipose depots. To determine the effects of obesity on adipose gene expression, male mice ( = 4) were fed a high-fat diet to induce obesity or a normal laboratory diet (lean controls) for 12-14 mo. Mesenteric VAT and inguinal SAT were isolated for bulk RNA sequencing. AT from lean controls served as a reference to obesity-induced changes. The long-term high-fat diet induced the expression of 169 and 814 unique genes in SAT and VAT, respectively. SAT from obese mice exhibited 308 differentially expressed genes (164 upregulated and 144 downregulated). VAT from obese mice exhibited 690 differentially expressed genes (262 genes upregulated and 428 downregulated). KEGG pathway and GO analyses revealed that metabolic pathways were upregulated in SAT versus downregulated in VAT while inflammatory signaling was upregulated in VAT. We next determined common genes that were differentially regulated between SAT and VAT in response to obesity and identified four genes that exhibited this profile: and were upregulated in SAT/downregulated in VAT while and were downregulated in SAT/upregulated in VAT. We propose that these genes in particular should be further pursued to determine their roles in SAT versus VAT with respect to obesity. A long-term high-fat diet induced the expression of more than 980 unique genes across subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The high-fat diet also induced the differential expression of nearly 1,000 AT genes. We identified four genes that were oppositely expressed in SAT versus VAT in response to the high-fat diet and propose that these genes in particular may serve as promising targets aimed at resolving VAT dysfunction in obesity.
内脏脂肪组织（VAT）的积累与心血管疾病和糖尿病密切相关。相比之下，那些皮下脂肪组织（SAT）增加而 VAT 没有相应增加的人，其代谢健康肥胖表型与肥胖相关。这些观察结果表明，功能失调的 VAT 是疾病进程的驱动因素，有必要研究肥胖引起的不同脂肪组织的改变。为了确定肥胖对脂肪基因表达的影响，雄性小鼠（n = 4）喂食高脂肪饮食以诱导肥胖或正常实验室饮食（瘦对照）12-14 个月。分离肠系膜 VAT 和腹股沟 SAT 进行批量 RNA 测序。瘦对照组的脂肪组织用作肥胖诱导变化的参考。长期高脂肪饮食分别诱导 SAT 和 VAT 中 169 和 814 个独特基因的表达。肥胖小鼠的 SAT 显示 308 个差异表达基因（164 个上调和 144 个下调）。肥胖小鼠的 VAT 显示 690 个差异表达基因（262 个上调和 428 个下调）。KEGG 通路和 GO 分析显示，代谢途径在 SAT 中上调，在 VAT 中下调，而炎症信号在 VAT 中上调。我们接下来确定了在 SAT 和 VAT 中对肥胖有差异调节的共同基因，并确定了四个表现出这种特征的基因：和在 SAT 中上调，在 VAT 中下调，而和在 SAT 中下调，在 VAT 中上调。我们提出，这些基因尤其应该进一步研究，以确定它们在 SAT 与 VAT 对肥胖的作用。长期高脂肪饮食诱导了超过 980 个独特基因在皮下脂肪组织（SAT）和内脏脂肪组织（VAT）中的表达。高脂肪饮食还诱导了近 1000 个脂肪基因的差异表达。我们确定了四个在 SAT 与 VAT 之间对高脂肪饮食有相反表达的基因，并提出这些基因尤其可能成为解决肥胖中 VAT 功能障碍的有前途的靶点。
