1. Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis
- Author
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Trico, D, Mengozzi, A, Nesti, L, Hatunic, M, Sanchez, Rg, Konrad, T, Lalic, K, Lalic, Nm, Mari, A, Natali, A, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Bohles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, Eh, Barthassat, V, Makoundou, V, Lehmann, Tno, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere, Ab, Louche-Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sanchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, I, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck-Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, F, Fanelli, C, Lucidi, P, Calcinaro, F, Saturni, A, Ferrannini, E, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhausl, W, Roden, M, Balkau, B, Dekker, Jm, Petrie, J, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, and Mota, L.
- Subjects
Adult ,Blood Glucose ,Male ,0301 basic medicine ,medicine.medical_specialty ,Subcutaneous adipose tissue ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,030209 endocrinology & metabolism ,Carbohydrate metabolism ,Palmitate ,NEFA ,Fatty Acids, Monounsaturated ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Insulin-Secreting Cells ,Internal medicine ,Adipokine ,Internal Medicine ,medicine ,Humans ,Palmitoleic acid ,Longitudinal Studies ,Monounsaturated fatty acid ,Lipokine ,Beta cell function ,Glucose tolerance ,Metabolism ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Insulin sensitivity ,Cross-Sectional Studies ,030104 developmental biology ,Endocrinology ,chemistry ,Body Composition ,Female ,Insulin Resistance ,Hormone - Abstract
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.
- Published
- 2019