Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes

Abstract

Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age‐ and gender‐ matched controls). Metabolic parameters were measured in the fasted state: body composition by dual‐energy X‐ray absorptiometry and insulin action by hyperinsulinemic–euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase‐PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor‐α (TNFα), macrophage inflammatory protein (MIP), interleukin‐8 (IL‐8)). Fasting glucose related to VAT expression of TNFα, MIP, serum amyloid A (SAA), IL‐1α, IL‐1β, IL‐8, and IL‐8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element–binding protein (CREBP), IL‐1β, and IL‐8. Insulin action related inversely to VAT complement C3 expression only. There were depot‐specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol‐binding protein‐4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.

Differential Patterns of Serum Concentration and Adipose Tissue Expression of Chemerin in Obesity: Adipose Depot Specificity and Gender Dimorphism

“…The existence of intrinsic, fat depot-specific functional differences in both humans and animal models has been strongly supported by the differential gene expression of adipokines, such as leptin (Montague et al, 1997;Van Harmelen et al, 1998), plasminogen activator inhibitor-1 (Alessi et al, 1997), interleukin-6 (Fried et al, 1998, retinol-binding protein-4 (RBP4), and adiponectin (Samaras et al, 2010). In contrast, differences in the expression of human chemerin in subcutaneous vs. visceral fat, or potential gender-related differences in the circulating and adipose tissue-specific expression of chemerin, have not been well characterized.…”

Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

“…Several of the proteins involved in innate and inflammatory responses have been found to be produced in adipose tissue, such as C-reactive protein (CRP), IL-6, and TNF-a (for review, see Fain, 2010;Fantuzzi, 2005), pointing to adipose tissue as being directly involved in maintaining or propagating low-grade inflammation as seen in obesity. Depot-specific differences in the gene expression profiles of adipose tissue [e.g., visceral adipose tissue (VAT) as opposed to subcutaneous adipose tissue (SAT)] have been demonstrated in diabetic human subjects (Samaras et al, 2010) and in apparently healthy obese women (Alvehus et al, 2010). Furthermore, nonabdominal SAT has been found to be less metabolically active and to even offer protection against lipotoxicity and fat deposition (for review, see Wronska and Kmiec, 2012).…”

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

“…Their expression and secretion in adipose tissue increase in metabolic disorders (Esser et al 2013). Their increased production could also explain the link between obesity and metabolic diseases (Samaras et al 2010, Ouchi et al 2011.…”

“…As pro-inflammatory factors that are also secreted from adipocytes, interleukins contribute to the chronic low-grade inflammatory state of adipose depots that is often observed in obesity and type 2 diabetes (Samaras et al 2010, Banerjee & Saxena 2012. Their expression and secretion in adipose tissue increase in metabolic disorders (Esser et al 2013).…”