Aims/hypothesis
Fatty acids of marine origin, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) act as hypolipidaemics, but
they do not improve glycaemic control in obese and diabetic patients. Thiazolidinediones like rosiglitazone are specific activators
of peroxisome proliferator-activated receptor γ, which improve whole-body insulin sensitivity. We hypothesised that a combined
treatment with a DHA and EPA concentrate (DHA/EPA) and rosiglitazone would correct, by complementary additive mechanisms,
impairments of lipid and glucose homeostasis in obesity.
Methods
Male C57BL/6 mice were fed a corn oil-based high-fat diet. The effects of DHA/EPA (replacing 15% dietary lipids), rosiglitazone
(10 mg/kg diet) or a combination of both on body weight, adiposity, metabolic markers and adiponectin in plasma, as well as
on liver and muscle gene expression and metabolism were analysed. Euglycaemic–hyperinsulinaemic clamps were used to characterise
the changes in insulin sensitivity. The effects of the treatments were also analysed in dietary obese mice with impaired glucose
tolerance (IGT).
Results
DHA/EPA and rosiglitazone exerted additive effects in prevention of obesity, adipocyte hypertrophy, low-grade adipose tissue
inflammation, dyslipidaemia and insulin resistance, while inducing adiponectin, suppressing hepatic lipogenesis and decreasing
muscle ceramide concentration. The improvement in glucose tolerance reflected a synergistic stimulatory effect of the combined
treatment on muscle glycogen synthesis and its sensitivity to insulin. The combination treatment also reversed dietary obesity,
dyslipidaemia and IGT.
Conclusions/interpretation
DHA/EPA and rosiglitazone can be used as complementary therapies to counteract dyslipidaemia and insulin resistance. The combination
treatment may reduce dose requirements and hence the incidence of adverse side effects of thiazolidinedione therapy.
Keywords Adiponectin - Diabetes - Docosahexaenoic acid - Eicosapentaenoic acid - Fish oil - Obesity - PPAR - Rosiglitazone - Thiazolidinedione
O. Kuda and T. Jelenik contributed equally to this work.
An erratum to this article can be found at
http://dx.doi.org/10.1007/s00125-009-1388-6