Decreased activity of desaturase 5 in association with obesity and insulin resistance aggravates declining long-chain n-3 fatty acid status in Cree undergoing dietary transition.

摘要

Emerging evidence shows that desaturase 5 ( Delta5), the key regulator in the synthesis of highly unsaturated long-chain fatty acids (HUFA), is modulated by factors including adiposity, diet and insulin resistance. This study explored the association of these factors in a cross-sectional study within a high-risk Cree population. Anthropometric measures and fasting blood glucose and insulin were analysed. Delta5 was estimated as the 20:4n-6:20:3n-6 ratio in erythrocyte membranes. The setting of the study was the Mistissini community in the Cree Territory of Quebec, Canada with 98 female and 68 male subjects aged 20-88 yr. Obesity (BMI >=30 kg/m2) was prevalent across age groups. Delta5 was inversely associated with BMI (Spearman's correlation coeff. (rs) -0.175; P = 0.03) and positively associated with age (rs 0.593; P < 0.0001), which was driven by age-related increases in dietary intake of n-3 fatty acids and decreases in 20:3n-6. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely associated with Delta5 in age-adjusted linear regression analyses in normoglycaemic individuals ( beta -2.110 (s.e. 0.566); P < 0.001), whereas no association was observed among glucose-intolerant individuals (interaction term P = 0.03). In contrast, there were no significant interactions indicating differences in the slope for each of the adiposity measures in their associations with Delta5. The study indicates that the dietary transition of reduced consumption of fish among younger Cree may compound the effects of obesity and emerging insulin resistance which, in turn, could reduce bioavailability of HUFA n-3 (through reduced Delta5 activity). Also, the study suggests that disease progression is an important consideration when evaluating correlates of Delta5 activity in observational studies.