Wessels 2015 Diabetes Obes Metab

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Wessels B, Ciapaite J, van den Broek NM, Houten SM, Nicolay K, Prompers JJ (2015) Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes. Diabetes Obes Metab 17:52-60.

» PMID: 25200673

Wessels B, Ciapaite J, van den Broek NM, Houten SM, Nicolay K, Prompers JJ (2015) Diabetes Obes Metab

Abstract: Pioglitazone improves peripheral insulin sensitivity in diabetes patients by redistributing lipids from muscle into adipose tissue. Mitochondria are thought to play a crucial role in the etiology of muscle insulin resistance. We aimed to determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function.

Lean, healthy and obese, diabetic Zucker diabetic fatty rats were treated with either pioglitazone (30 mg/kg/day) or water as a control (n = 6 per group), for 2 weeks. In vivo 1 H and 31 P magnetic resonance spectroscopy were performed on skeletal muscle to assess intramyocellular lipids (IMCL) and muscle oxidative capacity, respectively. Ex vivo muscle mitochondrial respiratory capacity and content were evaluated using high-resolution respirometry and citrate synthase activity assay, respectively.

IMCL content was 14-fold higher and in vivo muscle oxidative capacity was 26% lower in diabetic rats compared with lean rats, which was however not caused by impairments of ex vivo mitochondrial respiratory capacity or a lower mitochondrial content. Pioglitazone treatment restored in vivo muscle oxidative capacity in diabetic rats to the level of lean controls. This amelioration was not accompanied by an increase in mitochondrial content or ex vivo mitochondrial respiratory capacity, but rather was paralleled by an improvement in lipid homeostasis, i.e. lowering of plasma triglycerides and muscle lipid and long-chain acylcarnitine content.

Diminished in vivo muscle oxidative capacity in diabetic rats results from mitochondrial lipid overload and can be alleviated by redirecting the lipids from the muscle into adipose tissue using pioglitazone treatment.

Keywords: Antidiabetic drug, Energy regulation, Lipid-lowering therapy, PPAR-gamma agonist, Thiazolidinediones, Zucker Diabetic Fatty rat

O2k-Network Lab: NL Eindhoven Nicolay K, NL Groningen Reijngoud RJ


Labels: MiParea: Respiration  Pathology: Diabetes, Obesity 

Organism: Rat  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S  HRR: Oxygraph-2k