Plasma Fatty Acid Composition Was Associated with Apelin Gene Expression in Human Adipose Tissues

Background. Apelin is an adipokine with an intermediatory role in obesity and insulin resistance, which can be modified by dietary intake. Aims. In this study, we aimed to determine the association of the plasma fatty acid composition with apelin plasma concentration and gene expression in visceral (VAT) and subcutaneous (SAT) adipose tissues. Methods. In this cross-sectional study, we recruited 179 patients aged 19-75 years who were candidates for elective surgery. Through the surgery, SAT and VAT were collected to measure apelin gene expression. Anthropometric measurements, fasting blood samples, and dietary intakes were collected before surgery. Free fatty acids (FFAs) in fasting whole plasma were measured using gas chromatography with flame ionization detection. Linear regression models were used to estimate standardized β (STZ β ) showing the association of individual and total FFAs with apelin gene expression after adjustment for potential confounding variables. Results. In multivariable analysis, we observed a significant positive association of total plasma free fatty acids (FFAs) (STZ β = 0.241 , P = 0.006 ), saturated fatty acid (SFA) (STZ β = 0.336 , P < 0.001 ), and monounsaturated fatty acid (MUFA) (STZ β = 0.313 , P < 0.001 ) concentrations with apelin gene expression from VAT after controlling for age, sex, body mass index, homeostatic model assessment for insulin resistance (HOMA-IR), physical activity, and energy intake. In the SFA family, there was a direct association with plasma concentration of myristic acid (STZ β = 0.372 , P < 0.001 ), pentadecanoic acid ( STZ β = 0.252 , P = 0.002 ), and heptadecanoic acid (STZ β = 0.407 , P < 0.001 ) with apelin mRNA expression in VAT. There was no significant association between FFAs and apelin plasma concentration and SAT mRNA levels. Conclusions. In conclusion, circulating plasma FFAs, SFA, and MUFA had a positive association with apelin gene expression in VAT. It seems that plasma fatty acid composition may regulate apelin gene expression in VAT.

A plasma fatty acid profile associated to type 2 diabetes development: from the CORDIOPREV study

Purpose The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development. Methods We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score. Results FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04–3.37) in the Training set, and an HR of 2.14 (95% CI 1.50–2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (p < 0.05). Conclusion Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker. Clinical Trials.gov.Identifier NCT00924937.

Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People with Obesity

We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [¹⁸F]fluorodeoxyglucose and [¹⁵O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin-sensitive, and ii) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin-resistant but not in those who are insulin-sensitive. We found high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT, but was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest several putative SAT factors that are commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.

Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People with Obesity

We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [¹⁸F]fluorodeoxyglucose and [¹⁵O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin-sensitive, and ii) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin-resistant but not in those who are insulin-sensitive. We found high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT, but was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest several putative SAT factors that are commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.