Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue.

Abstract

Through analysis of mice with spatially and temporally restricted inactivation of Lpin1, we characterized its cell autonomous function in both white (WAT) and brown (BAT) adipocyte development and maintenance. We observed that the lipin 1 inactivation in adipocytes of aP2(Cre/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice resulted in lipodystrophy and the presence of adipocytes with multilocular lipid droplets. We further showed that time-specific loss of lipin 1 in mature adipocytes in aP2(Cre-ERT2/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice led to their replacement by newly formed Lpin1-positive adipocytes, thus establishing a role for lipin 1 in mature adipocyte maintenance. Importantly, we observed that the presence of newly formed Lpin1-positive adipocytes in aP2(Cre-ERT2/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice protected these animals against WAT inflammation and hepatic steatosis induced by a high-fat diet. Loss of lipin 1 also affected BAT development and function, as revealed by histological changes, defects in the expression of peroxisome proliferator-activated receptor alpha (PPARα), PGC-1α, and UCP1, and functionally by altered cold sensitivity. Finally, our data indicate that phosphatidic acid, which accumulates in WAT of animals lacking lipin 1 function, specifically inhibits differentiation of preadipocytes. Together, these observations firmly demonstrate a cell autonomous role of lipin 1 in WAT and BAT biology and indicate its potential as a therapeutical target for the treatment of obesity.

• Authors: Karim Nadra, Jean-Jacques Médard, Joram D Mul, Gil-Soo Han, Sandra Grès, Mario Pende, Daniel Metzger, Pierre Chambon, Edwin Cuppen, Jean-Sébastien Saulnier-Blache, George M Carman, Béatrice Desvergne, Roman Chrast
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 32 Issue 23 Pg. 4794-810 (Dec 2012) ISSN: 1098-5549 [Electronic] United States
• PMID: 23028044 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Nuclear Proteins
• Phosphatidic Acids
• Lpin1 protein, mouse
• Phosphatidate Phosphatase

Topics

• 3T3 Cells
• Adipocytes (cytology, metabolism)
• Adipose Tissue, Brown (cytology, metabolism)
• Adipose Tissue, White (cytology, metabolism)
• Animals
• Cell Differentiation
• Cell Line
• Cells, Cultured
• Diet, High-Fat (adverse effects)
• Gene Deletion
• Humans
• Mice
• Mice, Transgenic
• Nuclear Proteins (genetics, metabolism)
• Obesity (genetics, metabolism)
• Phosphatidate Phosphatase (genetics, metabolism)
• Phosphatidic Acids (metabolism)