The size of human subcutaneous adipocytes, but not adiposity, is associated with inflammation, endoplasmic reticulum stress, and insulin resistance markers.

BACKGROUND: The fat storage capacity of the adipose tissue prevents ectopic lipid deposition, which is one of the risk factors for metabolic abnormalities in obesity. This capacity depends upon the adipogenic gene expression and blood supply provision for tissue expansion through angiogenesis. Here, we studied hyperplasia/hypertrophy of subcutaneous white adipose tissue (scWAT) concerning adipogenic gene expression, angiogenic status, and metabolic parameters in non-obese and different classes of obese individuals. METHODS: The scWAT samples were collected from 80 individuals. The anthropometric parameters, adipose tissue cell size, serum biochemistry, ER stress-induced XBP1 splicing, PPARγ2, SFRP1, WNT10B, and VEGFA gene expression levels were studied. In addition, the CD31 level was investigated by Western blotting. RESULTS: The obese individuals had greater waist circumferences and higher serum TG, TC, insulin, and HOMA-IR than the non-obese group. However, the largest adipocyte size, increased TNFα, insulin, and HOMA-IR, and the highest expression level of sXBP1, WNT10B, and VEGFA were observed in Class I obese individuals. It means that inflammation, insulin resistance, and ER stress accompany hypertrophic scWAT adipocytes with limited adipose tissue expansion ability. Furthermore, the Class II + III obese individuals showed high PPARγ2 expression and CD31 levels. There is adipogenesis through hyperplasia in this group. The SFRP1 expression was not significantly different in the studied groups. CONCLUSION: The results suggest that the capability of adipogenesis with inadequate angiogenesis is related to the metabolic status, inflammation, and ER function. Therefore, therapeutic strategies that support both angiogenesis and adipogenesis can effectively prevent the complications of obesity.

Possible role of WNT10B in increased proliferation and tubule formation of human umbilical vein endothelial cell cultures treated with hypoxic conditioned medium from human adipocytes.

Regulation of angiogenesis plays an important role in adipose tissue expansion and function. The Wnt pathway and WNT10B, the main member of Wnt family, participate in angiogenesis in cancer tumors, but there is limited evidence to support the regulatory role of WNT10B in human adipose tissue angiogenesis. Subcutaneous white adipose tissue (scWAT) of 80 participants including obese and non-obese subjects was obtained and the expression of WNT10B and VEGFA genes were evaluated using qPCR. Human adipose-derived stem cells (hADSC) were differentiated to adipocytes and incubated under either hypoxic or normoxic conditions. The conditioned media of these adipocytes were collected and used as growth media for human umbilical vein endothelial cells (HUVEC) in Matrigel. We evaluated the proliferation, cell cycle phases, tubule formation and ß-catenin activation of these treated cells. We found a significant correlation between WNT10B and VEGFA expression in the scWAT of both obese and non-obese subjects. Proliferation and tubule formation of HUVEC treated with conditioned media of hypoxic adipocytes (hCM) in the S-phase were increased significantly compared to the HUVEC treated with the conditioned media of normoxic adipocytes (nCM). The expression of WNT10B and VEGFA was enhanced in hypoxic adipocytes compared to normoxic adipocytes; also, activation and nuclear translocation of ß-catenin was enhanced in the HUVEC treated with hCM compared to nCM. WNT10B acts as an angiogenic protein in scWAT under hypoxic conditions. Hypoxia induced WNT10B increases VEGFA expression and causes tube formation by HUVECs and angiogenesis in adipose tissue via the canonical Wnt/ß-catenin pathway.

Association of the 223A/G LEPR polymorphism with serum leptin levels in Iranian subjects with type 2 diabetes.

BACKGROUND: Leptin, an adipocyte-derived hormone, has a pivotal role in the regulation of body weight through acting on its specific leptin receptor (LEPR). The 223A/G polymorphism of the LEPR gene is one of the most common polymorphism in all populations.  In this study, we aimed to investigate the impact of the 223A/G polymorphism of the LEPR gene on serum levels of leptin in type 2 diabetes mellitus (T2DM) in a sample of Iranian population. MATERIALS AND METHODS: One hundred and forty-four T2DM patients were screened and compared to 147 healthy controls.  The 223A/G LEPR polymorphism was genotyped using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). The serum levels of leptin were measured. RESULTS: The mean serum levels of leptin in T2DM patients were significantly higher than that of healthy control subjects; 22.90 ng/ml (95 % confidence interval [CI] = 20.79 - 25.23) vs.  8.70 ng/ml (95 % CI = 7.87 - 9.63). The genotypes (AA, AG, and GG) distributions of the 223A/G polymorphism were 55.5 %, 41 %, and 3.5 % in T2DM and 54.4 %, 42.2 %, and 3.4 % in healthy controls. The results showed no significant differences in the 223A/G LEPR genotype and allele frequencies between T2DM and control subjects (χ2 = 0.043, P = 0.979 and χ2 = 0.003, P = 0.957), respectively. In addition, the serum leptin levels were markedly higher in subjects with GG genotype than those with AG or GG genotype only in T2DM CONCLUSION: The 223A/G LEPR gene polymorphism is associated with markedly increased serum leptin levels in T2DM. However, no differences were determined in genotype and allele frequencies between T2DM patients and control subjects.