422 Accelerated Adipose Tissue Dysfunction and Cardiovascular Risk in Individuals of South Asian Ethnicity

Abstract

BackgroundIndividuals with similar degrees of obesity can have significantly different risks of developing metabolic diseases. We previously identified that South Asians (SA) have more cardio-metabolic risk factors compared with European caucasians (EC) matched for body mass index (BMI). In the present study, we examined whether ethnic-specific differences in adipose tissue morphology and metabolic function can account for differences in cardiovascular disease (CVD) risk between SA and EC.MethodsSubcutaneous superficial abdominal adipose tissue biopsies were obtained from 108 males and females of SA or EC descent, with a mean age of 36 years overall, and assessed for adipose tissue: (1.) morphology; (2.) functional metabolic processes, determined through gene expression profiles; and (3.) endocrine functions, measured via serum adipokine levels. All values reported are adjusted for BMI, age and sex.ResultsAdipocyte diameter was significantly greater (259±4 vs. 238±5 units, P<0.01) among SA compared with EC. SA also expressed greater levels SREBP1, TIMP1 and CD68 mRNA than EC, indicating increased lipid accumulation, decreased extracellular matrix breakdown and increased macrophage accumulation and inflammation in SA, respectively. Finally, serum adiponectin levels, were markedly lower in SA compared with EC (by 37%, P<0.001), and was associated with hyperinsulinemia and a marked 4-fold greater hepatic fat accumulation (P<0.01).ConclusionSA have evidence of adipose tissue dysfunction at a relatively early age, as demonstrated by adipocyte hypertrophy, increased lipid accumulation and inflammation and reduced adiponectin secretion compared with EC. Adipose tissue dysfunction is related to greater CVD risk factors in SA and may be the primary defect leading to accelerated CVD and associated high morbidity and mortality rates in SA.AstraZeneca BackgroundIndividuals with similar degrees of obesity can have significantly different risks of developing metabolic diseases. We previously identified that South Asians (SA) have more cardio-metabolic risk factors compared with European caucasians (EC) matched for body mass index (BMI). In the present study, we examined whether ethnic-specific differences in adipose tissue morphology and metabolic function can account for differences in cardiovascular disease (CVD) risk between SA and EC. Individuals with similar degrees of obesity can have significantly different risks of developing metabolic diseases. We previously identified that South Asians (SA) have more cardio-metabolic risk factors compared with European caucasians (EC) matched for body mass index (BMI). In the present study, we examined whether ethnic-specific differences in adipose tissue morphology and metabolic function can account for differences in cardiovascular disease (CVD) risk between SA and EC. MethodsSubcutaneous superficial abdominal adipose tissue biopsies were obtained from 108 males and females of SA or EC descent, with a mean age of 36 years overall, and assessed for adipose tissue: (1.) morphology; (2.) functional metabolic processes, determined through gene expression profiles; and (3.) endocrine functions, measured via serum adipokine levels. All values reported are adjusted for BMI, age and sex. Subcutaneous superficial abdominal adipose tissue biopsies were obtained from 108 males and females of SA or EC descent, with a mean age of 36 years overall, and assessed for adipose tissue: (1.) morphology; (2.) functional metabolic processes, determined through gene expression profiles; and (3.) endocrine functions, measured via serum adipokine levels. All values reported are adjusted for BMI, age and sex. ResultsAdipocyte diameter was significantly greater (259±4 vs. 238±5 units, P<0.01) among SA compared with EC. SA also expressed greater levels SREBP1, TIMP1 and CD68 mRNA than EC, indicating increased lipid accumulation, decreased extracellular matrix breakdown and increased macrophage accumulation and inflammation in SA, respectively. Finally, serum adiponectin levels, were markedly lower in SA compared with EC (by 37%, P<0.001), and was associated with hyperinsulinemia and a marked 4-fold greater hepatic fat accumulation (P<0.01). Adipocyte diameter was significantly greater (259±4 vs. 238±5 units, P<0.01) among SA compared with EC. SA also expressed greater levels SREBP1, TIMP1 and CD68 mRNA than EC, indicating increased lipid accumulation, decreased extracellular matrix breakdown and increased macrophage accumulation and inflammation in SA, respectively. Finally, serum adiponectin levels, were markedly lower in SA compared with EC (by 37%, P<0.001), and was associated with hyperinsulinemia and a marked 4-fold greater hepatic fat accumulation (P<0.01). ConclusionSA have evidence of adipose tissue dysfunction at a relatively early age, as demonstrated by adipocyte hypertrophy, increased lipid accumulation and inflammation and reduced adiponectin secretion compared with EC. Adipose tissue dysfunction is related to greater CVD risk factors in SA and may be the primary defect leading to accelerated CVD and associated high morbidity and mortality rates in SA.AstraZeneca SA have evidence of adipose tissue dysfunction at a relatively early age, as demonstrated by adipocyte hypertrophy, increased lipid accumulation and inflammation and reduced adiponectin secretion compared with EC. Adipose tissue dysfunction is related to greater CVD risk factors in SA and may be the primary defect leading to accelerated CVD and associated high morbidity and mortality rates in SA.