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Oh D Y, et al., Gpr120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-Inflammatory and Insulin-Sensitizing Effects. Cell, 2010. 142(5): 687-98.

SYNOPSIS

Metabolon(Lipomics) results led to:

  • New therapeutic targets
  • Elucidation of the importance of omega-3 fatty acids within a high-fat diet paradigm


Key metabolomicobservations:

  • High fat diets lack omega-3 fatty acids as compared to chow diets
  • Omega-3 fatty acid stimulation of GPR120 ameliorates non-alcoholic fatty liver disease


Synopsis
Chronic tissue inflammation is an important mechanism causing insulin resistance. Omega-3 fatty acids exert potent insulin sensitizing effects through their anti-inflammatory actions. GPR120 are orphan G protein-coupled receptors and although it was appreciated GPR120 could bind long chain fatty acids, their physiological functions remained unknown. It was found that GPR120 is an omega-3 fatty acid receptor and the full signaling cascade was elucidated. GPR120 stimulation by omega-3 fatty acids reduced inflammatory macrophages in adipose tissue through inhibition of both the TLR and TNF-α inflammatory signaling pathways and increased insulin sensitivity. Further, GPR120 signaling by omega-3 fatty acids protected against non-alcoholic fatty liver disease. Thus, GPR120 is a key node in the integration of anti-inflammatory and insulin sensitizing responses and a potential therapeutic target for the treatment of insulin resistant diseases.

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