03584nas a2200481 4500008004100000022001400041245009300055210006900148260001300217300001100230490000700241520226000248653000902508653002202517653002102539653002002560653001602580653002102596653002202617653000902639653002602648653003302674653001102707653001502718653001102733653002302744653001502767653001102782653000902793653003202802653002402834653001702858653001602875653001802891100002502909700001702934700001902951700002402970700001902994700002403013700002903037856003603066 2010 eng d a1938-320700aCirculating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes.0 aCirculating palmitoleic acid and risk of metabolic abnormalities c2010 Dec a1350-80 v923 a

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 independent lifestyle correlates of higher palmitoleate concentrations. In multivariable analyses that adjusted for these factors and other potential confounders, higher palmitoleate concentrations were independently 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 divergent lifestyle determinants or endogenous sources (liver, adipose tissue) of fatty acid synthesis.

10aAged10aAged, 80 and over10aAlcohol Drinking10aBody Mass Index10aCholesterol10aCholesterol, HDL10aDiabetes Mellitus10aDiet10aDietary Carbohydrates10aFatty Acids, Monounsaturated10aFemale10aFibrinogen10aHumans10aInsulin Resistance10aLife Style10aLipids10aMale10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSex Factors10aTriglycerides1 aMozaffarian, Dariush1 aCao, Haiming1 aKing, Irena, B1 aLemaitre, Rozenn, N1 aSong, Xiaoling1 aSiscovick, David, S1 aHotamisligil, Gökhan, S uhttps://chs-nhlbi.org/node/123804243nas a2200433 4500008004100000022001400041245010700055210006900162260001600231300001000247490000800257520302000265653001403285653000903299653002303308653001603331653002103347653001903368653003003387653003303417653002103450653001103471653001103482653001403493653002303507653000903530653002403539653001703563653001803580653001803598100002503616700001703641700001903658700002403677700001903701700002403720700002903744856003603773 2010 eng d a1539-370400aTrans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.0 aTranspalmitoleic acid metabolic risk factors and newonset diabet c2010 Dec 21 a790-90 v1533 a

BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is 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: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.

DESIGN: Prospective cohort study from 1992 to 2006.

SETTING: Four U.S. communities.

PATIENTS: 3736 adults in the Cardiovascular Health Study.

MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.

RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 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.

LIMITATION: Results could be affected by measurement error or residual confounding.

CONCLUSION: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

10aAdiposity10aAged10aC-Reactive Protein10aCholesterol10aCholesterol, HDL10aDairy Products10aDiabetes Mellitus, Type 210aFatty Acids, Monounsaturated10aFeeding Behavior10aFemale10aHumans10aIncidence10aInsulin Resistance10aMale10aProspective Studies10aRisk Factors10aTriglycerides10aUnited States1 aMozaffarian, Dariush1 aCao, Haiming1 aKing, Irena, B1 aLemaitre, Rozenn, N1 aSong, Xiaoling1 aSiscovick, David, S1 aHotamisligil, Gökhan, S uhttps://chs-nhlbi.org/node/1257