Phenotyping Ethnic Differences in Body Fat Depots

There are remarkable ethnic differences in the incidence of metabolic syndrome associated features; including insulin resistance, type 2 diabetes, hypertension and cardiovascular diseases. Studies have suggested that South Asians (SA) present an unfavourable body fat phenotype, which includes a pattern of elevated visceral adipose tissue (VAT), and liver fat content; depots strongly associated with the progression of metabolic dysregulation. However, there are a limited number of studies examining body fat composition by ethnicity. The purpose of this thesis was to comprehensively phenotype VAT, abdominal subcutaneous adipose tissue (ASAT) and liver fat content in Caucasian (Cau), SA and Black African (BA) individuals from a large number of distinct populations. Here, I include data from three adult cohorts: the UK Biobank (n=9533) of mixed ethnicities, the DIRECT cohort (n=1553) of Cau pre-diabetic individuals and The West London Observation (TWLO) cohort (n=747) of mixed ethnicities. In addition, I present data from Pune Maternal Nutrition study (PMNS) cohort; comprising 423 young adults of SA descent in India. Analyses of body fat phenotype in Cau pre-diabetic populations showed higher VAT (mean differences= 0.5 litre, p<0.0001) and liver fat content (mean differences= 0.6%, p<0.0001), but lower ASAT (mean differences= -0.2 litre, p<0.0001) compared to Cau from the general population (free-living). I also observed negative associations between VAT, ASAT, liver fat content and day to day physical activity in both pre-diabetic and general populations (pre-diabetic; VAT; r= -0.296, ASAT; r= -0.163, liver fat: r= -0.186 and general population; VAT; r= -0.185, ASAT: r= -0.374, liver fat: r= -0.139, p<0.001 for all). Analysis of both the TWLO and UK Biobank revealed no differences in VAT or liver fat in SA in UK compared to other ethnic groups (TWLO; VAT: SA: 3.0 ± 1.6 litres, Cau: 3.3 ± 2.1 litres; liver fat: SA= 6.4 ± 11.1%, Cau= 6.5 ± 13.6%, p=ns - UK Biobank; VAT: SA: 3.6 ± 1.6 litres, Cau: 3.8 ± 1.5 litres; liver fat: SA: 4.6 ± 4.6%, Cau: 4.2 ± 4.6%, p=ns). Analysis of both these cohorts also revealed a more favourable body fat phenotype with BA males presenting significantly less VAT than SA and Cau males (p<0.05 for both). Data from the PMNS cohort revealed high levels of VAT in 18 year old India-based SA population. A high proportion (58.7%) of these lean individuals also presented with the thin-outside fat inside (TOFI) phenotype (a ratio of VAT to ASAT). A key finding is the lack of an unfavourable body fat phenotype in UK based SA. Therefore, the increased incidence of metabolic syndrome associated features in the SA population may arise via a mechanism unrelated to elevated levels of VAT or liver fat

Investigating the lipodystrophy genetic score associations with insulin sensitivity, ectopic and visceral fat in people at risk or with diabetes: a DIRECT study

Molecular Epidemiolog