Dataset Information

Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.

ABSTRACT:

Aims/hypothesis

During pregnancy, adipose tissue (AT) must expand to support the growing fetus and the future nutritional needs of the offspring. Limited expandability of AT is associated with insulin resistance, attributed to ectopic lipid deposition. This study aimed to investigate human AT expandability during pregnancy and its role in the pathogenesis of gestational diabetes mellitus (GDM).

Methods

This cross-sectional study of omental (OM) and subcutaneous (SQ) AT collected at Caesarean delivery included 11 pregnant and three non-pregnant women with normal glucose tolerance (NGT), five with GDM, three with type 2 diabetes mellitus. Adipocyte size, capillary density, collagen content and capillary growth were measured. Affymetrix arrays and real-time PCR studies of gene expression were performed.

Results

Mean OM adipocyte size was greater in women with GDM than in those with NGT (p?=?0.004). Mean OM and SQ capillary density was lower in GDM compared with NGT (p?=?0.015). Capillary growth did not differ significantly between groups. The most differentially expressed AT transcript when comparing non-pregnant and pregnant women corresponded to the IGF binding protein (IGFBP)-5, the expression levels of which was found by subsequent quantitative real-time PCR to be lower in women with GDM vs women with NGT (p?Conclusions/interpretationThe relative OM adipocyte hypertrophy and decreased OM and SQ capillary density are consistent with impaired AT expandability in GDM. The induction of adipose tissue IGFBP5 in pregnancy and its decrease in GDM point to the importance of the IGF-1 signalling pathway in AT expansion in pregnancy and GDM susceptibility.

SUBMITTER: Rojas-Rodriguez R

PROVIDER: S-EPMC4526585 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.

Rojas-Rodriguez Raziel R Lifshitz Lawrence M LM Bellve Karl D KD Min So Yun SY Pires Jacqueline J Leung Katherine K Boeras Crina C Sert Aylin A Draper Jacqueline T JT Corvera Silvia S Moore Simas Tiffany A TA

Diabetologia 20150613 9

<h4>Aims/hypothesis</h4>During pregnancy, adipose tissue (AT) must expand to support the growing fetus and the future nutritional needs of the offspring. Limited expandability of AT is associated with insulin resistance, attributed to ectopic lipid deposition. This study aimed to investigate human AT expandability during pregnancy and its role in the pathogenesis of gestational diabetes mellitus (GDM).<h4>Methods</h4>This cross-sectional study of omental (OM) and subcutaneous (SQ) AT collected a ...[more]

PMID: 26067361

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Project description:CONTEXT/OBJECTIVE:Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D. DESIGN/PATIENTS:Male patients with recently-diagnosed T2D and healthy male controls (CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass, and age (n?=?14 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry. We assessed mitochondrial efficiency (coupling: state 3/4o; proton leak: state 4o/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging. RESULTS:T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44%, and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (P?<?0.01) and AT IS (P?<?0.05), 73% and 31% higher HCL (P?<?0.05), and DSAT-thickness (P?<?0.001), but similar hepatic IS compared with CON. Mitochondrial efficiency was ~22% lower in SSAT and DSAT of T2D patients (P?<?0.001) and ~8% lower in SSAT vs DSAT (P?<?0.05). In both fat depots, mitochondrial coupling correlated positively with muscle IS and metabolic flexibility (r ? 0.40; P?<?0.05), proton leak correlated positively (r ? 0.51; P?<?0.01) and oxidative capacity negatively (r ? -0.47; P?<?0.05) with fasting free fatty acids (FFA). Metabolic flexibility correlated positively with SAT-oxidative capacity (r ? 0.48; P?<?0.05) and negatively with DSAT-thickness (r = -0.48; P?<?0.05). DSAT-thickness correlated negatively with mitochondrial coupling in both depots (r ? -0.50; P?<?0.01) and muscle IS (r = -0.59; P?<?0.01), positively with FFA during clamp (r?=?0.63; P?<?0.001) and HCL (r?=?0.49; P?<?0.01). CONCLUSIONS:Impaired mitochondrial function, insulin resistance, and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver.

Dataset Information

Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.

Aims/hypothesis

Methods

Results

Publications

Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.

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