TY - JOUR
T1 - Adipocyte lipin 1 expression associates with human metabolic health and regulates systemic metabolism in mice
AU - LaPoint, Andrew
AU - Singer, Jason M.
AU - Ferguson, Daniel
AU - Shew, Trevor M.
AU - Renkemeyer, M. Katie
AU - Palacios, Hector H.
AU - Field, Rachael L.
AU - Yerrathota, Sireesha
AU - Kumari, Roshan
AU - Shankaran, Mahalakshmi
AU - Smith, Gordon I.
AU - Yoshino, Jun
AU - He, Mai
AU - Patti, Gary J.
AU - Hellerstein, Marc K.
AU - Klein, Samuel
AU - Brestoff, Jonathan R.
AU - Morris, E. Matthew
AU - Finck, Brian N.
AU - Lutkewitte, Andrew J.
N1 - Publisher Copyright:
© 2024, LaPoint et al.
PY - 2024/12/2
Y1 - 2024/12/2
N2 - Dysfunctional adipose tissue is believed to promote the development of hepatic steatosis and systemic insulin resistance, but many of the mechanisms involved are still unclear. Lipin 1 catalyzes the conversion of phosphatidic acid to diacylglycerol, the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissue LPIN1 expression is decreased in people with obesity compared with lean subjects, and low LPIN1 expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multiomic phenotyping demonstrated that adipocyte-specific Lpin1-/- mice had a metabolically unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of metabolically associated steatohepatitis that was exacerbated by high-fat diets. We conclude that adipocyte lipin 1-mediated lipid storage is vital for preserving adipose tissue and systemic metabolic health, and its loss predisposes mice to metabolically associated steatohepatitis.
AB - Dysfunctional adipose tissue is believed to promote the development of hepatic steatosis and systemic insulin resistance, but many of the mechanisms involved are still unclear. Lipin 1 catalyzes the conversion of phosphatidic acid to diacylglycerol, the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissue LPIN1 expression is decreased in people with obesity compared with lean subjects, and low LPIN1 expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multiomic phenotyping demonstrated that adipocyte-specific Lpin1-/- mice had a metabolically unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of metabolically associated steatohepatitis that was exacerbated by high-fat diets. We conclude that adipocyte lipin 1-mediated lipid storage is vital for preserving adipose tissue and systemic metabolic health, and its loss predisposes mice to metabolically associated steatohepatitis.
UR - http://www.scopus.com/inward/record.url?scp=85211213598&partnerID=8YFLogxK
U2 - 10.1172/JCI169722
DO - 10.1172/JCI169722
M3 - Article
C2 - 39405118
AN - SCOPUS:85211213598
SN - 0021-9738
VL - 134
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 23
M1 - e169722
ER -