Obesity has both environmental and genetic factors, but the molecular mechanisms involved in fat deposition have been unclear. In June 17 Advanced Online Nature Medicine, Kazumasa Miyawaki and colleagues from Kyoto University, Kyoto, Japan, show that obesity is promoted via the gastric inhibitory polypeptide (GIP) signaling and inhibition of this pathway prevents fat deposition in mice (Nat Med 2002, DOI:10.1038/nm727).

GIP is a peptide released from duodenal cells after ingestion of fat or glucose. Miyawaki et al. engineered mice with an inactivated GIP receptor (GIPR) and observed that these animals were protected from both obesity and insulin resistance when fed a high-fat diet. In addition, the Gipr–/– mice had a lower respiratory quotient and used fat as the preferred energy substrate.

"Because the GIP promotes the efficient storage of ingested fat, its gene is metabolically thrifty, and may well play a pivotal role in the...

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