Background/Aims: GPR43 and GPR120 have recently been deorphanised as receptors for fatty acids. Fatty acids mediate a variety of metabolic processes in the body, however, the effect these receptors have on metabolism is not fully understood. Here, we characterise the effect of diet-induced obesity on the expression of GPR43 and GPR120 in tissues important in maintaining metabolic health. Methods: Six-week old male Sprague Dawley rats were fed either a high fat diet (HFD; 22% fat) or control diet (5% fat; n = 8-9/group) for 12 weeks. Rats were euthanized and the heart, liver, soleus and extensor digitorum longus (EDL) skeletal muscles were excised. GPR43 and GPR120 receptor abundance was quantified by ‘real-time’ PCR. Results: GPR43 mRNA abundance was significantly up-regulated by a HFD in liver and soleus and EDL skeletal muscles compared to control (p ≤ 0.05). Whilst a HFD significantly up-regulated GPR120 gene transcripts in cardiac tissue and EDL skeletal muscle when compare to control (p ≤ 0.05). Conclusion: We have shown for the first time that up-regulation of GPR43 and GPR120 in response to a HFD, is tissue specific. This suggests these receptors have different roles in mediating metabolic function in a number of tissues in the human body.

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These findings show that FAs induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors. This persistent difference in PDK4 expression, present after culturing, suggests a fundamental alteration in the FA-mediated gene expression. This may in turn translate to differences in the regulation of oxidative substrate flux to impact on insulin sensitivity.

Obesity is associated with increased body fat composition and elevated risk of metabolic and cardiovascular disease. The activity of the renin-angiotensin system is generally increased in obesity and experimental evidence has shown that angiotensin influences appetite and metabolism as well as mechanisms that induce adipose tissue growth and metabolism in peripheral organs. This review summarises some of the key evidence from animal and human experiments that links the renin-angiotensin system to obesity and metabolic disease. This research has been greatly aided by the continuing development of new pharmaceuticals that inhibit the renin-angiotensin system. While their primary use is in the treatment of hypertension and heart failure, a range of experimental and clinical evidence indicates their potential use in the treatment of obesity and metabolic disease.