Young Adult LEW.1WR1 Rats, a Model of Liver FAT10 Overexpression, Develop Insulin Resistance and Fatty Liver With Age

Autor: Madushika M Wimalarathne, Sharifa Love‐Rutledge, Luis Mercado, James Wolfsberger, Bernhard Vogler, Quiana C. Wilkerson Vidal, Victoria J McConnell
Rok vydání: 2021
Předmět:
Zdroj: Journal of the Endocrine Society
ISSN: 2472-1972
5313-5318
Popis: As human lifespan increases, comorbid conditions that impact quality of life have become a serious problem. FAT10 has been identified as a gene that when knocked out, improves age associated metabolic dysfunctions and increased longevity in mice (1). There is increased Fat10 expression in the liver in obesity (2,5). Providing evidence that fat10 expression may be important for triggering the transition to metabolic dysfunction in aging. Adult LEW.1WR1(1WR1) rats have increased body mass without excess abdominal fat mass compared to control rats (3). Yet, it was unclear where the excess mass was stored. We hypothesized that the 1WR1 rat would develop increased liver fat mass as a product of increased insulin resistance in response to increased liver fat10 expression over time. To test this hypothesis, we did insulin tolerance tests(7 weeks & 15 weeks), triglyceride assays, and histological analysis of the liver(23 weeks), in 1WR1 rats(n=7) and Wistar Furth (WF) rats(n=7) on control diets. We analyzed images using histological scoring for nonalcoholic fatty liver disease from the literature (4). We also assessed the slides for Mallory Denk bodies (MBs). The body mass of 1WR1 rats were increased compared to WF rat groups starting from the age of 7 weeks (391.4∓8.572g vs. 271.8∓11.62g; p (1) Canaan et al.,PNAS. April 2014; 111 (14): 5313-5318.(2)Vidal et al., FASEB.2020, 34: 1-1,(3) Collins et al., J Endocr Soc. 2019;3(1),(4).Kleiner et al., Hepatology, 2005; 41 (6): 1313–1321,(5).Dali-Youcef et al., Hepatol Commun. 2019;3(9):1205-1220.
Databáze: OpenAIRE