(P16-042-23) Combined Effect of Albumin Deficiency and Acute Exercise in Reducing Hepatic Lipid Accumulation in Mice

Objectives: Hepatic lipid droplets (LDs) are implicated in the progression of ectopic lipid deposition. The core of LDs, triacylglycerol (TG) is synthesized from the esterification of fatty acids to a glycerol-3-phosphate (G-3-P) backbone. Albumin transports free fatty acids in plasma, and we previously showed mice with albumin deficiency exhibit lower hepatic TG levels. Exercise is accepted as a beneficial strategy to alter hepatic metabolism, and each individual bout of exercise likely affects the liver. However, it is still unknown how hepatic LDs are impacted by acute exercise. Taken together, we aimed to study the combined effect of albumin deficiency and acute exercise on hepatic LD abundance, sizes, and localization.

Methods: Eight-week-old male albumin knockout (Alb^-/-) mice and wildtype (WT) mice were divided into the sedentary group and exercise group. Exercised mice performed a 30-minute high-intensity exercise bout (n = 6). Transmission electron microscopy and biochemical assays were conducted to reveal the changes and relations in hepatic LDs, glycogen and mitochondria.

Results: We found that sedentary Alb^-/- mice had lower abundance and size in hepatic LD, highly associated with mitochondria, while WT mice exhibited higher abundance and larger size in hepatic LDs (P < 0.0001), surrounded by glycogen granules. Following acute exercise, hepatic LDs in Alb^-/- mice reduced in size while those in WT mice grew larger (percentage change: -40.03 % versus +13.90 %, P < 0.0001). Moreover, the growth of hepatic LD in WT was associated with elevated G-3-P concentration in the liver (P < 0.05), potentially derived from glycogen (correlation between percentage change in glycogen and lipid area density: R = -0.32, P < 0.05). The reduction in LDs in Alb^-/- mice was potentially due to low glycogen levels.

Conclusions: In conclusion, Alb^-/- mice exhibited an enhanced capacity for reduced hepatic LD abundance in response to exercise. The findings suggest that modulating albumin’s functions in combination with exercise could be a potential strategy to reduce ectopic lipid deposition.

Funding Sources: The work was supported by a grant from the Ralph W. and Grace M. Showalter Research Trust, as well as by support from the McKinley Educational Initiative.