Differential Gene Expression of Subcutaneous Adipose Tissue among Lean, Obese, and after RYGB (Different Timepoints): Systematic Review and Analysis

Abstract

The main roles of adipose tissue include triglycerides storage and adipokine secretion, which regulate energy balance and inflammation status. In obesity, adipocyte dysfunction leads to proinflammatory cytokine production and insulin resistance. Bariatric surgery is the most effective treatment for obesity, the gold-standard technique being Roux-en-Y gastric bypass (RYGB). Since metabolic improvements after RYGB are clear, a better understanding of adipose tissue molecular modifications could be derived from this study. Thus, the aim of this systematic review was to find differentially expressed genes in subcutaneous adipose tissue of lean, obese and post-RYGB (distinct timepoints). To address this objective, publications from 2015-2022 reporting gene expression (candidate genes or transcriptomic approach) of subcutaneous adipose tissue from lean and obese individuals before and after RGYB were searched in PubMed, Elsevier, and Springer Link. Excluded publications were reviews, studies analyzing serum, other types of tissues, or bariatric procedures. A risk-of-bias summary was created for each paper using Robvis, to finally include 17 studies. Differentially expressed genes in post-RYGB vs. obese and lean vs. obese were obtained and the intersection among these groups was used for analysis and gene classification by metabolic pathway. Results showed that the lean state as well as the post-RYGB is similar in terms of increased expression of insulin-sensitizing molecules, inducing lipogenesis over lipolysis and downregulating leukocyte activation, cytokine production and other factors that promote inflammation. Thus, massive weight loss and metabolic improvements after RYGB are accompanied by gene expression modifications reverting the "adipocyte dysfunction" phenomenon observed in obesity conditions.

Keywords: RYGB; gene candidate; gene expression; obesity; subcutaneous adipose tissue; transcriptome.

Figure 3

Subcutaneous adipose tissue candidate gene expression among lean, obese, and post-RYGB (different timepoints). Comparison of expression levels of each gene among different studies, identified by the Calculated fold change was significant (p-value < 0.05, ▲, ●) or not (p-value > 0.05, △, ○). (α: [38]; ☨: [47]; Ω: [51]; λ: [41]; Τ: [44]; γ: [40]; η: [46]; θ: [49]; ϕ: [42]; ρ: [43]; ᴪ: [48]; δ: [34]; Π: [50]; Σ: [32]; ε: [31]).

Figure 1

Systematic review flowchart. Identification, eligibility, inclusion, gene identification and analysis, using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).

Figure 2

Subcutaneous adipose tissue differentially expressed genes using a candidate gene approach. Genes that were studied at least in two papers in post-RYGB vs. obese (yellow) and lean vs. obese (pink) are represented. Gene classification by function: glucose metabolism (orange), lipid metabolism (purple), endocrine function (green), and inflammation (blue).

Figure 4

Subcutaneous adipose tissue differentially expressed genes using a transcriptomic gene approach. Genes that were differentially expressed in at least two microarrays in post-RYGB vs. obese and were found in lean vs. obese are represented. Gene classification by function: lipid and aminoacid metabolism, glycerol transport, acetyl-COA and acyl-COA metabolic process, cell surface, signaling transduction, apoptosis signaling. In addition, inflammation and immune system pathways such as: anti-inflammatory response, innate immune system, inflammation mediated by chemokine and cytokine signaling, interleukins signaling, leukocyte activation and involve in immune response, regulation of leukocyte differentiation, antigen processing cross presentation, neutrophil degranulation, phagocytic cells, and regulation of cytokine production.

Figure 5

Subcutaneous adipose tissue transcriptomic gene expression among lean, obese, and post-RYGB (different timepoints). Comparison of expression levels of each gene among different studies, identified by the author (☨: [47]; Ω: [51]; λ: [41]; Τ: [44]; ᴪ: [48]; Π: [50]; Σ: [32]). Calculated fold change was significant (p-value < 0.05, ▲, ●) or not (p-value > 0.05, △, ○).

Figure 5

Subcutaneous adipose tissue transcriptomic gene expression among lean, obese, and post-RYGB (different timepoints). Comparison of expression levels of each gene among different studies, identified by the author (☨: [47]; Ω: [51]; λ: [41]; Τ: [44]; ᴪ: [48]; Π: [50]; Σ: [32]). Calculated fold change was significant (p-value < 0.05, ▲, ●) or not (p-value > 0.05, △, ○).

Figure 5

Subcutaneous adipose tissue transcriptomic gene expression among lean, obese, and post-RYGB (different timepoints). Comparison of expression levels of each gene among different studies, identified by the author (☨: [47]; Ω: [51]; λ: [41]; Τ: [44]; ᴪ: [48]; Π: [50]; Σ: [32]). Calculated fold change was significant (p-value < 0.05, ▲, ●) or not (p-value > 0.05, △, ○).