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Adipocyte lipin 1 expression associates with human metabolic health and regulates systemic metabolism in mice
Andrew LaPoint, … , Brian N. Finck, Andrew J. Lutkewitte
Andrew LaPoint, … , Brian N. Finck, Andrew J. Lutkewitte
Published October 15, 2024
Citation Information: J Clin Invest. 2024;134(23):e169722. https://doi.org/10.1172/JCI169722.
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Research Article Hepatology Metabolism Article has an altmetric score of 9

Adipocyte lipin 1 expression associates with human metabolic health and regulates systemic metabolism in mice

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Abstract

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.

Authors

Andrew LaPoint, Jason M. Singer, Daniel Ferguson, Trevor M. Shew, M. Katie Renkemeyer, Hector H. Palacios, Rachael L. Field, Sireesha Yerrathota, Roshan Kumari, Mahalakshmi Shankaran, Gordon I. Smith, Jun Yoshino, Mai He, Gary J. Patti, Marc K. Hellerstein, Samuel Klein, Jonathan R. Brestoff, E. Matthew Morris, Brian N. Finck, Andrew J. Lutkewitte

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Figure 3

Adn-Lpin1–/– mice have similar metabolic energetics to WT mice.

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Adn-Lpin1–/– mice have similar metabolic energetics to WT mice.
Eight-we...
Eight-week old male mice were fed an LFD (n = 5–8) or HFD (n = 7–10) for 5 weeks before indirect calorimetry analysis. Mice were acclimated for 5 days before metabolic measurements. (A) Body weight changes over 8 days of indirect calorimetry housing. (B) Energy intake averaged over 8 days calculated as kcal/g/24 h. (C–H) All data were calculated as the 24-hour average over the last 3 days of indirect calorimetry housing. (C–E) Total energy expenditure (EE), resting EE, and non-resting EE were calculated as the 24-hour average for the last 3 days. (F) Respiratory quotient (RQ) (VCO2/VO2). (G and H) Activity was calculated as average beam breaks (X, Y, and Z). All data are expressed as means ± SEM, and significance was determined by 2-way ANOVA with post hoc Tukey’s multiple-comparisons tests. †P < 0.05 for LFD vs. HFD (n = 5–10).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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