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Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes.

ABSTRACT: Our aim was to examine longitudinal associations of triacylglyceride fatty acid (TGFA) composition with insulin sensitivity (IS) and ?-cell function. Adults at risk for T2D (n = 477) had glucose and insulin measured from a glucose challenge at three time points over 6 years. The outcome variables Matsuda insulin sensitivity index, homeostatic model of assessment 2-percent sensitivity (HOMA2-%S), Insulinogenic Index over HOMA-IR (IGI/IR), and Insulin Secretion-Sensitivity Index-2 were computed from the glucose challenge. Gas chromatography quantified TGFA composition from the baseline. We used adjusted generalized estimating equation (GEE) models and partial least squares (PLS) regression for the analysis. In adjusted GEE models, four TGFAs (14:0, 16:0, 14:1n-7, and 16:1n-7 as mol%) had strong negative associations with IS, whereas others (e.g., 18:1n-7, 18:1n-9, 20:2n-6, and 20:5n-3) had strong positive associations. Few associations were seen for ?-cell function, except for 16:0, 18:1n-7, and 20:2n-6. PLS analysis indicated four TGFAs (14:0, 16:0, 14:1n-7, and 16:1n-7) that clustered together and strongly related with lower IS. These four TGFAs also correlated highly (r > 0.4) with clinically measured triacylglyceride. We found that higher proportions of a cluster of four TGFAs strongly related with lower IS as well as hypertriglyceridemia, suggesting that only a few FAs within the TGFA composition may primarily explain lipids' role in glucose dysregulation.

SUBMITTER: Johnston LW

PROVIDER: S-EPMC6121925 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes.

Johnston Luke W LW Liu Zhen Z Retnakaran Ravi R Zinman Bernard B Giacca Adria A Harris Stewart B SB Bazinet Richard P RP Hanley Anthony J AJ

Journal of lipid research 20180709 9

Our aim was to examine longitudinal associations of triacylglyceride fatty acid (TGFA) composition with insulin sensitivity (IS) and β-cell function. Adults at risk for T2D (n = 477) had glucose and insulin measured from a glucose challenge at three time points over 6 years. The outcome variables Matsuda insulin sensitivity index, homeostatic model of assessment 2-percent sensitivity (HOMA2-%S), Insulinogenic Index over HOMA-IR (IGI/IR), and Insulin Secretion-Sensitivity Index-2 were computed fr ...[more]

PMID: 29986954

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Project description:BackgroundPreviously, a "purchase" pattern (rich in vegetable oil, manufactured foods, red meat and poultry, fruits, and vegetables) was identified among adults in urban Ghana and was inversely associated with T2D, while a "traditional" pattern (rich in fish, palm oil, plantain, green-leafy vegetables, beans, garden egg, fermented maize products,) increased the odds of T2D. To investigate, if specific fatty acids (FAs), partly reflecting the intakes of certain food groups and cooking methods, might explain the observed diet-disease relationships, serum phospholipid fatty acid profiles were characterized and their relationships with blood lipids that are common risk factors for T2D were analyzed.MethodsThe relative proportions of 28 FAs (%) in 653 Ghanaians without T2D were measured by gas chromatography. In a cross-sectional analysis, the associations of FAs with dietary patterns and with serum lipids that are likely involved in T2D development were investigated. The FAs distributions across dietary pattern scores were examined. Standardized beta coefficients (β) were calculated for the associations of dietary pattern scores (per 1 standard deviation (SD) increase) with FAs. Across the tertiles of selected diet-related FAs, adjusted means of serum triglycerides, cholesterol, HDL-cholesterol and LDL-cholesterol were calculated.ResultsIn this mainly female (76%), middle-aged (mean age: 46.4, SD: 15.3 years) and predominately overweight study population (mean body mass index: 25.8, SD: 5.4 kg/m2), saturated FAs (SFAs) contributed 52% to total serum FAs, n-6 polyunsaturated FAs (PUFAs) 27%, monounsaturated FAs 12%, n-3 PUFAs 9% and trans FAs (TFAs) <1%. The "purchase" pattern was related to lower proportions of n-3 PUFAs (β per 1 score SD: -0.25, p < 0.0001), but higher proportions of linoleic acid (LA) (β per 1 score SD: 0.24, p < 0.0001). The "traditional" pattern was characterized by lower proportions of arachidic acid (β per 1 score SD: -0.10, p = 0.001). LA was inversely associated with triglycerides, but positively with HDL-cholesterol and LDL-cholesterol.ConclusionsIn this Ghanaian population, serum FA profiles reflected the intake of key components of dietary patterns, such as fish and vegetable oil. FAs from manufactured foods (SFAs) and deep-fried meals (TFAs) did not contribute to the observed associations between dietary patterns and T2D. Still, LA might partly explain the health-beneficial effect of the "purchase" pattern.

Project description:RationaleLong chain fatty acids (LCFAs) are the preferred substrate for energy provision in hearts. However, the contribution of endogenous triacylglyceride (TAG) turnover to LCFA oxidation and the overall dependence of mitochondrial oxidation on endogenous lipid is largely unstudied.ObjectiveWe sought to determine the role of TAG turnover in supporting LCFA oxidation and the influence of the lipid-activated nuclear receptor, proliferator-activated receptor (PPAR)alpha, on this balance.Methods and resultsPalmitoyl turnover within TAG and palmitate oxidation rates were quantified in isolated hearts, from normal mice (nontransgenic) and mice with cardiac-specific overexpression of PPARalpha (MHC-PPARalpha). Turnover of palmitoyl units within TAG, and thus palmitoyl-coenzyme A recycling, in nontransgenic (4.5+/-2.3 micromol/min per gram dry weight) was 3.75-fold faster than palmitate oxidation (1.2+/-0.4). This high rate of palmitoyl unit turnover indicates preferential oxidation of palmitoyl units derived from TAG in normal hearts. PPARalpha overexpression augmented TAG turnover 3-fold over nontransgenic hearts, despite similar fractions of acetyl-coenzyme A synthesis from palmitate and oxygen use at the same workload. Palmitoyl turnover within TAG of MHC-PPARalpha hearts (16.2+/-2.9, P<0.05) was 12.5-fold faster than oxidation (1.3+/-0.2). Elevated TAG turnover in MHC-PPARalpha correlated with increased mRNA for enzymes involved in both TAG synthesis, Gpam (glycerol-3-phosphate acyltransferase, mitochondrial), Dgat1 (diacylglycerol acetyltransferase 1), and Agpat3 (1-acylglycerol-3-phospate O-acyltransferase 3), and lipolysis, Pnliprp1 (pancreatic lipase related protein 1).ConclusionsThe role of endogenous TAG in supporting beta-oxidation in the normal heart is much more dynamic than previously thought, and lipolysis provides the bulk of LCFA for oxidation. Accelerated palmitoyl turnover in TAG, attributable to chronic PPARalpha activation, results in near requisite oxidation of LCFAs from TAG.

Dataset Information

Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes.

Publications

Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes.

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