Science

Dariush Mozaffarian, MD DrPH, Haiming Cao, PhD, Irena B. King, PhD, Rozenn N. Lemaitre, PhD MPH, Xiaoling Song, PhD, David S. Siscovick, MD MPH, and Gökhan S. Hotamisligil, MD PhD

Background:
Palmitoleic acid (cis-16:1n-7), produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.
Objective:
We investigated whether circulating trans-palmitoleate was independently related to lower metabolic risk and incident type2 diabetes.
Design:
Prospective cohort study (1992–2006).
Setting:
Four US communities.
Patients:
3,736 adults in the Cardiovascular Health Study.
Measurements:
Plasma phospholipid fatty acids, anthropometry, blood lipids, inflammatory markers, and glucose-insulin levels were measured at baseline in 1992; and diet, 3 years earlier. In multivariable-adjusted models, we investigated how demographic, clinical, and lifestyle factors independently related to trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). We validated findings for metabolic risk factors in an independent cohort of 327 women.
Results:
In multivariable-analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate. Higher trans-palmitoleate was associated with slightly lower adiposity and, independently, higher high-density-lipoprotein(HDL)-cholesterol (across quintiles: +1.9%, P=0.04), lower triglycerides (−19.0%, P less than 0.001), lower total:HDL-cholesterol (−4.7%, P less than 0.001), lower C-reactive protein (−13.8%, P=0.05), and lower insulin resistance (−16.7%, P less than 0.001). Trans-palmitoleate was associated with substantially lower incidence of diabetes, with multivariable-hazard-ratios=0.41 (95%CI=0.27–0.64) and 0.38 (95%CI=0.24–0.62) in quintile-4 and quintile-5, versus quintile-1 (P-trend less than 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.
Limitations:
Measurement error; residual confounding.
Conclusions:
Circulating trans-palmitoleate is associated with lower insulin resistance, atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support need for detailed further experimental and clinical investigation.
Primary Funding Source:
National Institutes of Health.