Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis

Anil K Agarwal; Katie Tunison; Jay D Horton; Abhimanyu Garg

doi:10.1016/j.isci.2024.109517

Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis

iScience. 2024 Mar 26;27(4):109517. doi: 10.1016/j.isci.2024.109517. eCollection 2024 Apr 19.

Authors

Anil K Agarwal^{1

2}, Katie Tunison^{1

2}, Jay D Horton^{2

3}, Abhimanyu Garg^{1

2}

Affiliations

¹ Section of Nutrition and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.
² Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390, USA.
³ Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

Both humans and mice with congenital generalized lipodystrophy due to AGPAT2 deficiency develop diabetes mellitus, insulin resistance, and hepatic steatosis, which have been attributed to the near total loss of adipose tissue (AT). Here, we show that regulated AT regeneration in doxycycline (dox)-fed Tg^-AT-hAGPAT2;mAgpat2^-/- mice partially ameliorates hepatic steatosis at 12 weeks of age and causes reduced expression of genes involved in hepatic de novo lipogenesis despite partial (∼30-50%) AT regeneration compared to that in wild-type mice. Compared to chow-fed Tg^-AT-hAGPAT2;mAgpat2^-/- mice, those fed dox diet had markedly reduced serum insulin levels, suggesting an improvement in insulin resistance. Interestingly, the fasting plasma glucose levels in dox-fed Tg^-AT-hAGPAT2;mAgpat2^-/- mice were no different than those in chow-fed wild-type mice. Indirect calorimetry revealed normalization in the energy balance of dox-fed Tg^-AT-hAGPAT2;mAgpat2^-/- mice compared to that in chow-fed mice. This study's findings suggest that partial AT regeneration in lipodystrophic mice can ameliorate metabolic derangements.

Keywords: Lipid; Pathophysiology; Physiology.

Abstract

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