Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis
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.
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.
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).
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.
KeywordsAdipokine Beta cell function Glucose tolerance Insulin sensitivity Lipokine Monounsaturated fatty acid NEFA Palmitate Palmitoleic acid Subcutaneous adipose tissue
Percentage fat mass
Impaired fasting glucose
Impaired glucose tolerance
Monounsaturated fatty acid
Normal glucose tolerance
Oral glucose insulin sensitivity index
Percentage palmitoleate enrichment in the total NEFA pool
Polyunsaturated fatty acid
Relationship between Insulin Sensitivity and Cardiovascular disease study
Saturated fatty acid
- std. β
Standardised regression coefficient
Preliminary study findings were presented as an abstract at the 55th EASD Annual Meeting in Barcelona, Spain, in 2019.
DT contributed to study design, data analysis and interpretation and writing the manuscript. AMe, LN, MH, RGS, TK, KL and NML contributed to data collection and edited the manuscript. AM undertook the mathematical modelling of insulin secretion and beta cell function variables, contributed to data interpretation and edited the manuscript. AN contributed to study design and supervision, securing of funding, and data collection, analysis and interpretation, and edited and critically revised the manuscript. All authors read and approved the final submitted version of the manuscript. DT and AN are the guarantors of this work and, as such, have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
The RISC study was partly supported by European Union grant QLG1-CT-2001-01252. DT is funded by the European Foundation for the Study of Diabetes (EFSD) Mentorship Programme.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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