Pitere, Reabetswe R.Van Heerden, Marlene B.Pepper, Michael SeanAmbele, Melvin Anyasi2022-07-192022-07-192022-02Pitere, R.R.; Van Heerden, M.B.; Pepper, M.S.; Ambele, M.A. Slc7a8 Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs. Biology 2022, 11, 311. https://doi.org/10.3390/ biology11020311.2079-7737 (online)10.3390/ biology11020311https://repository.up.ac.za/handle/2263/86294Supplementary Materials: Supplementary method S1: Genotyping of mice, Figure S1: Mice in study, Figure S2: Adipocyte hypertrophy at 5 weeks, Figure S3: Lipid droplets in the liver at 5 weeks, Figure S4: Perimuscular adipose tissue in gastrocnemius muscle at 5 weeks, Figure S5: Accumulation of adipose tissue in the lungs, Figure S6: Adipocyte diameter between white adipose tissue depots.Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of in vitro adipogenesis in human adipose-derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. The current study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. slc7a8 knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On the HFD, both WT and KO mice (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WTHFD. KOHFD had significantly reduced levels of glucose intolerance compared with those observed in WTHFD. KOHFD also had significantly reduced adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal, and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD had decreased lipid accumulation in the liver, heart, gastrocnemius muscle, lung, and kidney. This study demonstrates that targeting slc7a8 protects against diet-induced obesity by reducing lipid accumulation in multiple organs and suggests that if targeted, has the potential to mitigate the development of obesity-associated comorbiditiesen© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.ObesityAdipose tissueAdipogenesisLipid accumulationSLC7A8Fat depotsTissue histologyArticle