Changes in apolipoprotein abundance dominate proteome responses to prolonged fasting in elephant seals

Abstract

Unlike many animals that reduce activity during fasting, northern elephant seals (NES) undergo prolonged fasting during energy-intensive life-history stages such as reproduction and molting, fueling fasting energy needs by mobilizing fat stores accrued during foraging. NES display several unique metabolic features such as high fasting metabolic rates, elevated blood lipid and high-density lipoprotein (HDL) cholesterol levels, efficient protein sparing and resistance to oxidative stress during fasting. However, the cellular mechanisms that regulate these adaptations are still not fully understood. To examine how metabolic coordination is achieved during prolonged fasting, we profiled changes in blubber, skeletal muscle and plasma proteomes of adult female NES over a 5 week fast associated with molting. We found that while blubber and muscle proteomes were remarkably stable over fasting, over 50 proteins changed in abundance in plasma, including those associated with lipid storage, mobilization, oxidation and transport. Apolipoproteins dominated the blubber, plasma and muscle proteome responses to fasting. APOA4, APOE and APOC3, which are associated with lipogenesis and triglyceride accumulation, decreased, while APOA1, APOA2 and APOM, which are associated with lipid mobilization and HDL function, increased over fasting. Our findings suggest that changes in apolipoprotein composition may underlie the maintenance of high HDL levels and, together with adipokines and hepatokines that facilitate lipid catabolism, may mediate the metabolic transitions between feeding and fasting in NES. Many of these proteins have not been previously studied in this species and provide intriguing hypotheses about metabolic regulation during prolonged fasting in mammals.

Mirror image serum lipid carrier protein profiles in pup and lactating mother Atlantic grey seals reflect contrasting resource mobilisation challenges

“…Our fasting mother grey seals show broadly similar results to those from fasting, moulting adult female elephant seals in which plasma Apo-CIII and ApoE decreased with time, and Apo-I increased, although we did not see a decrease in Apo-IV and an increase in Apo-AII (Khudyakov et al, 2022). While both species were fasting during the sampling periods, fasting during lactation (when milk production is important) and fasting during moulting are likely to involve different apolipoprotein dynamics.…”

Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal

“…The northern elephant seal has been used in such physiological studies for decades ( Houser et al, 2013 ). Based primarily on fatty acid stratification data from this and other pinniped species ( Louis et al, 2014 ), we typically use the inner half of blubber biopsies collected from elephant seals in our analyses of blubber responses to physiological stressors ( Deyarmin et al, 2019 ; Khudyakov et al, 2022 ). However, the physical boundary between these layers is not visually apparent, and blubber from elephant seals has not been included in previous morphological studies ( Gabler-Smith et al, 2022 ).…”