Obesity and body fat distribution

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A multitude of studies have shown that excess fat in the abdominal region (visceral adipose tissue) is strongly associated with metabolic alterations such as disturbed plasma lipoprotein profile, hyperinsulinaemia, insulin resistance and glucose intolerance. In comparative analyses, people of Black ancestry have the highest levels of generalized obesity (BMI >30kgm-2) and Mexican-Americans have the highest percentage body fat, but the highest levels of central obesity (as measured by waist: hip ratio) are found among South Asians and Mexican-Americans compared with European White, Chinese and Black-origin groups (Misra and Vikram, 2004). Whether these differences are attributable to diet, lack of exercise, genetic factors or a combination of these has not yet been established.

A recent study found that transgenic mice selectively overexpressing 11P-hydroxysteroid dehydrogenase type 1 (11BHSD-1) in adipose tissue developed abdominal obesity and exhibited insulin-resistant diabetes (Masuzaki etal., 2001). Extrapolating this to humans one might speculate that 11BHSD-1 activity is raised in the adipose tissue of groups such as South Asians, leading them to develop central obesity and the metabolic syndrome (Das, 2002). If this was the case, then peroxisome proliferator-activated receptor-gamma (PPARy) ligands, which markedly reduce 11BHSD-1 activity in vitro and in vivo and preferentially reduce abdominal fat, may be the drug of choice in groups such as South Asians.

There is an increasing body of evidence that insulin resistance may depend on levels of triglyceride stores in muscle cells (intramyocellular lipid) (Phillips etal, 1996; Krssak etal., 1999; Machann etal., 2004). Studies comparing triglyceride stores in muscle in different ethnic groups may help to establish whether this can account for ethnic variation in insulin resistance. However, we are aware of only two published studies that have examined this in South Asians (Forouhi etal, 1999; Misra etal, 2003), including the work of our group (Forouhi etal, 1999), and both studies failed to find an association between intramyocellular triglyceride and insulin sensitivity in South Asians, although lack of statistical power cannot be ruled out. This work should be repeated in other studies and in other ethnic groups.

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