Abstract
GPR120 (Ffar4) has been postulated to represent an important receptor mediating the improved metabolic profile seen upon ingestion of a diet enriched in polyunsaturated fatty acids (PUFAs). GPR120 is highly expressed in the digestive system, adipose tissue, lung and macrophages and also present in the endocrine pancreas. A new Gpr120 deficient mouse model on pure C57bl/6N background was developed to investigate the importance of the receptor for long-term feeding with a diet enriched with fish oil. Male Gpr120 deficient mice were fed two different high fat diets (HFDs) for 18 weeks. The diets contained lipids that were mainly saturated (SAT) or mainly n-3 polyunsaturated fatty acids (PUFA). Body composition, as well as glucose, lipid and energy metabolism, was studied. As expected, wild type mice fed the PUFA HFD gained less body weight and had lower body fat mass, hepatic lipid levels, plasma cholesterol and insulin levels and better glucose tolerance as compared to those fed the SAT HFD. Gpr120 deficient mice showed a similar improvement on the PUFA HFD as was observed for wild type mice. If anything, the Gpr120 deficient mice responded better to the PUFA HFD as compared to wild type mice with respect to liver fat content, plasma glucose levels and islet morphology. Gpr120 deficient animals were found to have similar energy, glucose and lipid metabolism when fed HFD PUFA compared to wild type mice. Therefore, GPR120 appears to be dispensable for the improved metabolic profile associated with intake of a diet enriched in n-3 PUFA fatty acids.
Highlights
GPR120 is a G-protein coupled receptor that is highly expressed in the human and rodent digestive system, notably, though not exclusively, in enteroendocrine Lcells [1]
The targeting strategy of the mouse Gpr120 gene is described under S1 Supplementary experimental procedures and illustrated in S1A Fig. In short, a 0.567 kb fragment of the coding sequence (CDS) within exon 1 was replaced in frame by a nuclear bGal expression cassette and a loxP floxed PGKneo selection marker gene
Gpr120 deficiency was confirmed by RT-PCR analyses, designed to amplify fragments both within and outside the deleted DNA sequence, using RNA derived from skeletal muscle, liver and lung tissue from wild type, heterozygous and homozygous Gpr120 KO mice
Summary
GPR120 is a G-protein coupled receptor that is highly expressed in the human and rodent digestive system, notably, though not exclusively, in enteroendocrine Lcells [1]. GPR120 mediates free fatty acid (FFA) stimulated release of glucagon-like peptide 1 (GLP1) that increases glucose stimulated insulin secretion (GSIS), enhances b-cell mass and reduces gastric emptying and appetite [2]. In addition to its role in the intestine, GPR120 is expressed in adipose tissue, lung, pro-inflammatory macrophages and islets of Langerhans [2, 4,5,6]. GPR120 was recently shown to be expressed in the delta-cells of the islets of Langerhans mediating a negative effect on glucose stimulated somatostatin secretion [7] as well as in alpha-cells mediating the fatty acid induced secretion of glucagon [8]. The most potent GPR120 ligands are n-3 polyunsaturated fatty acids (PUFAs), such as a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [5, 11]. N-6 PUFA and saturated fatty acids are able to activate the receptor [2, 8]
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