Premium
Differential Transcription of CD95 in Abdominal and Lower‐Body Subcutaneous Fat Depot–Implications for Regional Differences in Adipose Tissue Function
Author(s) -
Singh Prachi,
Zhang Yuebo,
Somers Virend K
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.752.6
Subject(s) - adipose tissue , endocrinology , medicine , leptin , adipokine , white adipose tissue , intra abdominal fat , obesity , insulin resistance , visceral fat
Background Abdominal (ABD) and lower‐body (LB) fat depots exert opposing effects on cardiometabolic risk factors. However, molecular mechanisms underlying these differences are not completely understood. Studies suggest an inflammatory role of CD95 in obesity‐associated adipose tissue inflammation and dysfunction. Also, leptin deficiency is associated with increased CD95 expression. Objective To examine the expression of CD95 in the ABD and LB fat depots and to investigate leptin‐dependent CD95 regulation. Methods Transcription of CD95 and other adipokines was determined in paired subcutaneous abdominal (ABD) and lower‐body (femoral, LB) fat samples obtained from 29 healthy individuals (10 females, age: 29.4 ± 7.6 years, BMI: 24 ± 4.1 kg/m 2 ). The underlying mechanisms and down‐stream effects of altered CD95 expression were evaluated using differentiated human white preadipocytes (dHWP). Results Reduced mRNA expression of CD95 was apparent in adipose tissue obtained from LB fat depot [ABD: 4.30 (13.91 – 0.06), LB: 2.49 (10.88 – 0.04), p = 0.01]. mRNA expression of MCP1 [ABD: 0.51 (1.35 – 0.34), LB: 0.51 (1.21 – 0.28), p = 0.51], CCL5 [ABD: 6.60 (43.45 – 1.40), LB: 4.44 (11.28 – 1.27), p = 0.20], TNFα [ABD: 1.10 (6.14 – 0.03), LB: 0.07 (5.84 – 0.03), p = 0.30], and leptin [ABD: 21.86 (31.33 – 14.6), LB: 27.23 (41.69 – 20.35), p = 0.08] was not different between the two fat depots. A positive relationship between CD95 mRNA and other inflammatory cytokines was evident in both ABD (MCP1: ρ = 0.79, p < 0.001; CCL5: ρ = 0.83, p < 0.001; TNFα: ρ = 0.87, p < 0.001) and LB fat depot (MCP1: ρ = 0.87, p < 0.001; CCL5: ρ = 0.78, p < 0.001; TNFα: ρ = 0.83, p < 0.001). Furthermore, leptin‐dependent decreases in CD95 mRNA (p = 0.04) and protein expression (p = 0.03) was seen in dHWP. Also, 24 hour pre‐treatment of dHWP with leptin protected cells from FasL (p = 0.03) induced apoptosis. Conclusions Compared to ABD adipose tissue, LB fat has reduced transcription of CD95. Additionally, expression of CD95 mRNA was associated with increased expression of inflammatory cytokines in both ABD and LB subcutaneous fat. Moreover, we show that leptin may mediate decreases in CD95 expression thereby protecting adipose tissue from FasL mediated apoptosis. Our studies suggest that the decreased CD95 mRNA expression in LB fat depot may be related to higher localized leptin expression and possibly contribute to depot specific alterations in adipose tissue function and consequent cardiometabolic risk. Support or Funding Information Prachi Singh is supported by AHA grant‐in‐Aid 17GRNT33660138. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .