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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Maria J
MJ
Pereira
AstraZeneca R&D, Mölndal, Sweden; Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Stanko
S
Skrtic
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Petros
P
Katsogiannos
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Niclas
N
Abrahamsson
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Cherno O
CO
Sidibeh
AstraZeneca R&D, Mölndal, Sweden.
Santosh
S
Dahgam
AstraZeneca R&D, Mölndal, Sweden.
Marianne
M
Månsson
Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Ulf
U
Risérus
Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Joel
J
Kullberg
Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: jan.eriksson@medsci.uu.se.
Jan W
JW
Eriksson
D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis*; D050152:Intra-Abdominal Fat; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
Adipose tissue; Lipid storage; Lipolysis; Metabolism; Type 2 diabetes