Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis

Abstract

Aims/hypothesis Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or 'lipokine') to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Methods Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic-euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Results Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = −0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). Conclusions/interpretation We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.

Positional and Compositional Analysis of Saturated, Monounsaturated and Polyunsaturated Fatty acids in Human Adipose Tissue Triglyceride by 13C NMR

“…No reuse allowed without permission. correlated with fat mass but was also positively correlated with insulin sensitivity after adjustment for age, sex and adiposity (24). These and other studies support a possible role of PO as a beneficial lipokine: its release from adipose tissue improves insulin sensitivity in other tissues (25).…”

“…In a study of overweight subjects, the molar fraction of PO in VLDL-TG was found to be positively correlated with elevated liver fat (23). In a cohort of nondiabetic subjects, Trico et al found that circulating non-esterified PO in the fasted state was positively correlated with fat mass but was also positively correlated with insulin sensitivity after adjustment for age, sex and adiposity (24). These and other studies support a possible role of PO as a beneficial lipokine: its release from adipose tissue improves insulin sensitivity in other tissues (25).…”

Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways

“…The body weight in cPOA group had no significant change, and reduced the hepatic steatosis, but fat index of that showed an increasing trend; The obvious interpretation was that the hepatic fat was mobilized by cPOA and stored in the adipose tissues. It was especially relevant given that some reports had shown a positive correlation between serum concentration of cPOA and adiposity, high level TG (Djousse et al, 2012;Luan et al, 2018;Trico et al, 2020). While, the body weight and fat index in tPOA group showed decreasing trend, but had no significant effect on hepatic steatosis, therefore we speculated tPOA increased hepatic lipid oxidation and export and increased thermogenesis in the brown adipose tissues (Wang, 2008).…”

“…Conversion of cholesterol to bile salts provides the major route for cholesterol elimination from the body. The initial and ratelimiting step in this pathway is catalyzed by 7ahydroxylase (Luan et al, 2018;Trico et al, 2020). The liver converts cholesterol into BAs via a series of reactions, including esterification.…”

Enrichment of palmitoleic acid by a combination of crystallization and molecular distillation

“…This fatty acid has demonstrated a wide range of applications in nutrition, medicine and chemical industries (Luan et al, 2018). For example, in animal models of metabolic disease, adipose tissue has been shown to release palmitoleic acid, which suppresses hepatic steatosis and improves insulin sensitivity (Trico et al, 2019). Consequently, palmitoleic acid has been in the spotlight as a promising anti-inflammatory lipid that may help ameliorate metabolic disorders (Cao et al, 2008).…”