Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors

• Published in: Metabolism, clinical and experimental Vol. 65; no. 12; pp. 1768 - 1780
• Main Authors: Pereira, Maria J, Skrtic, Stanko, Katsogiannos, Petros, Abrahamsson, Niclas, Sidibeh, Cherno O, Dahgam, Santosh, Månsson, Marianne, Risérus, Ulf, Kullberg, Joel, Eriksson, Jan W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adiposity; Aged; Case-Control Studies; Clinical Medicine; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Fatty Acids, Nonesterified - blood; Female; Glycated Hemoglobin A - analysis; Humans; Hyperglycemia - diagnosis; Intra-Abdominal Fat; Klinisk medicin; Lipid Metabolism; Lipid storage; Lipolysis; Male; Metabolism; Middle Aged; Sex Factors; Type 2 diabetes; Type 2 diabetes; Adipose tissue; PDHA1; IRS1; MRI; SAT; T2D; Lipid storage; VAT; LPL; Metabolism; Lipolysis; ADRA2A; AT; FABP4; FASN; NEFA; GLUT4 and SLC2A4
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2016.09.008

Elevated levels of circulating non-esterified fatty acids (NEFA) mediate many adverse metabolic effects. In this work we aim to determine the impact of type 2 diabetes (T2D), glycemic control and obesity on lipolysis regulation. 20 control and 20 metformin-treated T2D subjects were matched for sex (10M/10 F), age (58±11 vs 58±9 y) and BMI (30.8±4.6 vs 30.7±4.9kg/m2). In vivo lipolysis was assessed during a 3h-OGTT with plasma glycerol and NEFA levels. Subcutaneous adipose tissue (SAT) biopsies were obtained to measure mRNA and metabolite levels of factors related to lipolysis and lipid storage and to assess in vitro lipolysis in isolated subcutaneous adipocytes. Plasma NEFA AUC during the OGTT where higher 30% (P=0.005) in T2D than in control subjects, but plasma glycerol AUC and subcutaneous adipocyte lipolysis in vitro were similar, suggesting that adipose tissue lipolysis is not altered. Expression in SAT of genes involved in lipid storage (FABP4, DGAT1, FASN) were reduced in T2D subjects compared with controls, but no differences were seen for genes involved in lipolysis. T2D subjects had elevated markers of beta-oxidation, α-hydroxybutyrate (1.4-fold, P<0.01) and β-hydroxybutyrate (1.7-fold, P<0.05) in plasma. In multivariate analysis, HbA1c, visceral adipose tissue volume and sex (male) were significantly associated with NEFA AUC in T2D subjects. In T2D subjects, NEFA turnover is impaired, but not due to defects in lipolysis or lipid beta-oxidation. Impaired adipose NEFA re-esterification or de novo lipogenesis is likely to contribute to higher NEFA plasma levels in T2D. The data suggest that hyperglycemia and adiposity are important contributing factors for the regulation of plasma NEFA concentrations.