Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes

Background Animal experiments suggest that circulating palmitoleic acid (cis 16 1n-7) from adipocyte de novo fatty acid synthesis may directly regulate insulin resistance and metabolic dysregulation Objective We investigated the independent determinants of circulating palmitoleate in free living humans and whether palmitoleate is related to lower metabolic risk and the incidence of diabetes Design In a prospective cohort of 3630 US men and women in the Cardiovascular Health Study plasma phospholipid fatty acids anthropometric variables blood lipids inflammatory markers and glucose and insulin concentrations were measured between 1992 and 2006 by using standardized methods Independent determinants of plasma phospholipid palmitoleate and relations of palmitoleate with metabolic risk factors were investigated by using multivariable adjusted linear regression Relations with incident diabetes (296 incident cases) were investigated by using Cox proportional hazards Results The mean (+/- SD) palmitoleate value was 0 49 +/- 0 20% (range 0 11-2 55%) of total fatty acids Greater body mass index carbohydrate intake protein intake and alcohol use were each in dependent lifestyle correlates of higher palmitoleate concentrations In multivariable analyses that adjusted for these factors and other potential confounders higher palmitoleate concentrations were in dependently associated with lower LDL cholesterol (P < 0 001) higher HDL cholesterol (P < 0 001) lower total HDL cholesterol ratio (P = 0 04) and lower fibrinogen (P < 0 001) However palmitoleate was also associated with higher triglycerides (P < 0 001) and (in men only) with greater insulin resistance (P < 0 001) Palmitoleate was not significantly associated with incident diabetes Conclusions Adiposity (energy imbalance) carbohydrate consumption and alcohol use-even within typical ranges-are associated with higher circulating palmitoleate concentrations Circulating palmitoleate is robustly associated with multiple metabolic risk factors but in mixed directions perhaps related to diver gent lifestyle determinants or endogenous sources (liver adipose tissue) of fatty acid synthesis An, J Clin Nutr 2010 92 1350-8