Lipocalin 13 protein protects against hepatic steatosis by both inhibiting lipogenesis and stimulating fatty acid β-oxidation.

Abstract

Obesity is associated with hepatic steatosis, partially due to increased lipogenesis and decreased fatty acid β-oxidation in the liver; however, the underlying mechanism of abnormal lipid metabolism is not fully understood. We reported previously that obesity is associated with LCN13 (lipocalin 13) deficiency. LCN13 is a lipocalin family member involved in glucose metabolism, and LCN13 deficiency appears to contribute to hyperglycemia in obese mice. Here, we show that LCN13 is also an important regulator of lipogenesis and β-oxidation in the liver. In primary hepatocytes, recombinant LCN13 directly suppressed lipogenesis and increased fatty acid β-oxidation, whereas neutralization of endogenous LCN13 had an opposite effect. Transgenic overexpression of LCN13 protected against hepatic steatosis in mice with either dietary or genetic (ob/ob) obesity. LCN13 transgenic overexpression also improved hyperglycemia, glucose intolerance, and insulin resistance in ob/ob mice. Short-term LCN13 overexpression via an adenovirus-mediated gene transfer similarly attenuated hepatic steatosis in db/db mice. LCN13 inhibited the expression of important lipogenic genes and stimulated the genes that promote β-oxidation. These results suggest that LCN13 decreases liver lipid levels by both inhibiting hepatic lipogenesis and stimulating β-oxidation. LCN13 deficiency is likely to contribute to fatty liver disease in obese mice.

• Authors: Liang Sheng, Kae Won Cho, Yingjiang Zhou, Hong Shen, Liangyou Rui
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 44 Pg. 38128-38135 (Nov 04 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 21908604 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• Fatty Acids
• Lipids
• Lipocalins
• Recombinant Proteins
• lipocalin-13 protein, mouse
• Luciferases

Topics

• Animals
• Culture Media, Conditioned (pharmacology)
• Disease Models, Animal
• Fatty Acids (chemistry)
• Fatty Liver (metabolism, pathology)
• Insulin Resistance
• Lipids (chemistry)
• Lipocalins (metabolism)
• Luciferases (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Mice, Transgenic
• Recombinant Proteins (chemistry)
• Transgenes