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.