Omega-7 Abstracts 2

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The importance of palmitoleic acid to adipocyte insulin resistance and whole-body insulin sensitivity in type 1 diabetes

         (Bergman, Howard et al. 2013) Download

CONTEXT: Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat. OBJECTIVE: The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose. DESIGN, PATIENTS, AND METHODS: Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) . min. Infusions of [1,1,2,3,3-(2)H(2)]glycerol and [1-(13)C]palmitate were used to quantify lipid metabolism. RESULTS: Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes. CONCLUSIONS: Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population.


Is there something special about palmitoleate?

         (Hodson and Karpe 2013) Download

PURPOSE OF REVIEW: The fatty acid, palmitoleate (16:1 n - 7), has received a lot of attention in recent years for being 'lipokine' and for the first time, we review the evidence to determine if there is something special about palmitoleate in humans. RECENT FINDINGS: Despite dietary intakes being low (<4% of total energy) palmitoleate is the second most abundant monounsaturated fatty acid in most, but not all, blood lipid pools and notably more abundant in adipose tissue. Thus, compared with other fatty acids, the palmitoleate content of lipid pools must be influenced by endogenous synthesis, which appears to be tissue and depot specific. We present a summary of dietary intervention studies of food components enriched in palmitoleate but this gives inconclusive results in regards to an impact on human metabolic regulation. SUMMARY: To date, there is no strong evidence from human studies suggesting that palmitoleate has 'lipokine' effects. However, unlike other fatty acids, there is a clear tendency towards compartmentalization and tissue-specific formation of palmitoleate, which is intriguing and requires further investigation.

High levels of stearic acid, palmitoleic acid, and dihomo-gamma-linolenic acid and low levels of linoleic acid in serum cholesterol ester are associated with high insulin resistance

         (Kurotani, Sato et al. 2012) Download

The association of fatty acid composition with insulin resistance and type 2 diabetes has been reported in Western populations, but there is limited evidence of this association among the Japanese, whose populace consume large amounts of fish. To test the hypothesis that high palmitic, palmitoleic, and dihomo-gamma-linolenic acids and low levels of linoleic and n-3 fatty acids are associated with higher insulin resistance among the Japanese, the authors investigated the relationship between serum fatty acid composition and serum C-peptide concentrations in 437 Japanese employees aged 21 to 67 years who participated in a workplace health examination. Serum cholesterol ester and phospholipid fatty acid compositions were measured by gas-liquid chromatography. Desaturase activity was estimated by fatty acid product-to-precursor ratios. A multiple regression was used to assess the association between fatty acid and C-peptide concentrations. C-peptide concentrations were associated inversely with linoleic acid levels in cholesterol ester and phospholipid (P for trend = .01 and .02, respectively) and positively with stearic and palmitoleic acids in cholesterol ester (P for trend =.02 and .006, respectively) and dihomo-gamma-linolenic acid in cholesterol ester and phospholipid (P for trend < .0001 for both). C-peptide concentrations were not associated with n-3 polyunsaturated fatty acids. C-peptide concentrations significantly increased as delta-9-desaturase (16:1 n-7/16:0) and delta-6-desaturase (18:3 n-6/18:2 n-6) increased (P for trend = .01 and .03, respectively) and delta-5-desaturase (20:4 n-6/20:3 n-6) decreased (P for trend = .004). In conclusion, a fatty acid pattern with high levels of serum stearic, palmitoleic, or dihomo-gamma-linolenic acids; delta-9-desaturase (16:1 n-7/16:0) or delta-6-desaturase (18:3 n-6/18:2 n-6) activities; and low levels of serum linoleic acid or delta-5-desaturase (20:4 n-6/20:3 n-6) activity might be associated with higher insulin resistance in Japanese adults.

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

         (Mozaffarian, Cao et al. 2010) Download

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.

Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study

         (Mozaffarian, Cao et al. 2010) Download

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.

trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA)

         (Mozaffarian, de Oliveira Otto et al. 2013) Download

BACKGROUND: Dairy consumption is linked to a lower risk of type 2 diabetes, but constituents responsible for this relation are not established. Emerging evidence suggests that trans-palmitoleate (trans 16:1n-7), a fatty acid in dairy and also partially hydrogenated oils, may be associated with a more favorable metabolic profile and less incident diabetes. OBJECTIVE: We investigated the association of trans-palmitoleate with metabolic risk and incident diabetes in a multiethnic US cohort. DESIGN: Phospholipid fatty acids and metabolic risk factors were measured in 2000-2002 among 2617 adults in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of white, black, Hispanic, and Chinese Americans. In 2281 participants free of baseline diabetes, we also prospectively assessed the risk of new-onset diabetes (205 cases) from baseline to 2005-2007. RESULTS: trans-Palmitoleate concentrations correlated positively with self-reported consumption of whole-fat dairy, butter, margarine, and baked desserts and with other circulating biomarkers of both dairy fat and partially hydrogenated oil consumption, which suggested mixed dietary sources. After multivariable adjustment, trans-palmitoleate concentrations were associated with higher LDL cholesterol (quintile 5 compared with quintile 1: +6.4%; P-trend = 0.005), lower triglycerides (-19.1%; P-trend < 0.001), lower fasting insulin (-9.1%; P-trend = 0.002), and lower systolic blood pressure (-2.4 mm Hg; P-trend = 0.01). In prospective analyses, trans-palmitoleate was independently associated with lower incident diabetes (P-trend = 0.02), including a 48% lower risk in quintile 5 compared with quintile 1 (HR: 0.52; 95% CI: 0.32, 0.85). All findings were similar between men and women and between different race-ethnic subgroups. CONCLUSIONS: Circulating trans-palmitoleate is associated with higher LDL cholesterol but also with lower triglycerides, fasting insulin, blood pressure, and incident diabetes in a multiethnic US cohort. Our findings support the need for further experimental and dietary intervention studies that target circulating trans-palmitoleate. The MESA trial was registered at clinicaltrials.gov as NCT00005487.


References

Bergman, B. C., D. Howard, et al. (2013). "The importance of palmitoleic acid to adipocyte insulin resistance and whole-body insulin sensitivity in type 1 diabetes." J Clin Endocrinol Metab 98(1): E40-50. [PMID: 23150678]

Hodson, L. and F. Karpe (2013). "Is there something special about palmitoleate?" Curr Opin Clin Nutr Metab Care 16(2): 225-31. [PMID: 23324899]

Kurotani, K., M. Sato, et al. (2012). "High levels of stearic acid, palmitoleic acid, and dihomo-gamma-linolenic acid and low levels of linoleic acid in serum cholesterol ester are associated with high insulin resistance." Nutr Res 32(9): 669-675 e3. [PMID: 23084639]

Mozaffarian, D., H. Cao, et al. (2010). "Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes." Am J Clin Nutr 92(6): 1350-8. [PMID: 20943795]

Mozaffarian, D., H. Cao, et al. (2010). "Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study." Ann Intern Med 153(12): 790-9. [PMID: 21173413]

Mozaffarian, D., M. C. de Oliveira Otto, et al. (2013). "trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA)." Am J Clin Nutr 97(4): 854-61. [PMID: 23407305]