Genetic Manipulation of Obesity Mouse Models

All animal experiments were performed following the approval and guidelines of the Institutional Animal Care and Use Committee of Indiana University. Animals are maintained in accordance with the applicable portions of the Animal Welfare act and the DHHS Guide for the Care and Use of Laboratory Animals. LIPTER(Tg) C57BL/6J mice were generated using CRISPR/Cas9 at the Genome Editing, Transgenic, and Virus Core at UPMC Magee-Women’s Research Institute. Six-week-old male homozygous Lepr^db/db mice were obtained from the Jackson Laboratory (strain number 000697). Myh10 floxed mice with C57BL/6J background were obtained from Dr Robert S. Adelstein lab at Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute^{57 (link)}. C57BL/6J Tnnt2^Cre mice were obtained from Dr Chenleng Cai lab at Indiana University. Conditional Myh10^cKO in mouse CMs was generated by crossing Myh10^f/f mice with Tnnt2^MerCreMer mice. Six-week-old male Myh10^f/f and Myh10^f/f/Tnnt2^MerCreMer mice were injected with tamoxifen (0.1 mg g⁻¹ body weight) for days 1, 3 and 5 by intraperitoneal injection and then fed with a HFD (45 kcal% fat, Research Diets Inc., D12451i) for 3 months. Six-week-old male LIPTER(Tg) mice and age-matched WT C57BL/6J mice were fed with a HFD (45 kcal% fat, Research Diets Inc., D12451i) or NC (18 protein, Inotiv, 2018sx) for 10 months.