Changes in Northern Elephant Seal Skeletal Muscle Following Thirty Days of Fasting and Reduced Activity

Abstract

Northern elephant seals (NES, Mirounga angustirostris ) undergo an annual molt during which they spend ∼40 days fasting on land with reduced activity and lose approximately one-quarter of their body mass. Reduced activity and muscle load in stereotypic terrestrial mammalian models results in decreased muscle mass and capacity for force production and aerobic metabolism. However, the majority of lost mass in fasting female NES is from fat while muscle mass is largely preserved. Although muscle mass is preserved, potential changes to the metabolic and contractile capacity are unknown. To assess potential changes in NES skeletal muscle during molt, we collected muscle biopsies from 6 adult female NES before the molt and after ∼30 days at the end of the molt. Skeletal muscle was assessed for respiratory capacity using high resolution respirometry, and RNA was extracted to assess changes in gene expression. Despite a month of reduced activity, fasting, and weight loss, skeletal muscle respiratory capacity was preserved with no change in OXPHOS respiratory capacity. Molt was associated with 162 upregulated genes including those favoring lipid metabolism. We identified 172 downregulated genes including those coding for ribosomal proteins and genes associated with skeletal muscle force transduction and glucose metabolism. Following ∼30 days of molt, NES skeletal muscle metabolic capacity is preserved although mechanotransduction may be compromised. In the absence of exercise stimulus, fasting-induced shifts in muscle metabolism may stimulate pathways associated with preserving the mass and metabolic capacity of slow oxidative muscle.

Ontogeny of Carbon Monoxide-Related Gene Expression in a Deep-Diving Marine Mammal

“…Alternatively, expression of these genes may be decoupled from the CO pathway in NES, potentially due to their unique metabolic adaptations to prolonged fasting and the role of PGC1A in promoting lipid oxidation in muscle (Gudiksen and Pilegaard, 2017). However, muscle PGC1A expression in NES muscle did not vary with fasting state in this or other studies (Wright et al, 2020), and its role in fasting and diving adaptations of NES requires further investigation.…”

Elephant seal muscle cells adapt to sustained glucocorticoid exposure by shifting their metabolic phenotype

“…Recent work suggests that fasting-induced shifts in muscle metabolism stimulate pathways associated with preserving muscle mass in elephant seals (26), whereas earlier studies show that administration of exogenous ACTH upregulates catabolic genes in elephant seal skeletal muscle (28,29). Here, we generated a cellular model to study the mechanisms that drive tolerance to sustained glucocorticoid exposure in elephant seal muscle.…”

“…During these natural prolonged fasting periods, elephant seals rely primarily on lipid metabolism and endogenous glucose production to support metabolism in glucose-dependent tissues (19,20). Notably, prolonged fasting in elephant seals increases the levels of circulating cortisol, the primary glucocorticoid in pinnipeds (21)(22)(23)(24)(25), without inducing muscle atrophy (26). Previous studies show a 20fold range of individual serum cortisol concentrations with 2-to 3-fold increases in mean concentrations across natural fasts (20,22), but acute and repeated responses to exogenous ACTH suggest a much higher capacity for endogenous release (27).…”

Elephant seal muscle cells adapt to sustained glucocorticoid exposure by shifting their metabolic phenotype

“…During these natural prolonged fasting periods, elephant seals rely primarily on lipid metabolism and endogenous glucose production to support metabolism in glucose-dependent tissues (Champagne, Crocker, Fowler, & Houser, 2012; Crocker, Champagne, Fowler, & Houser, 2014). Notably, prolonged fasting in elephant seals increases the levels of circulating cortisol, the primary glucocorticoid in pinnipeds (Champagne, Houser, & Crocker, 2006; Jelincic, Tift, Houser, & Crocker, 2017; Khudyakov et al, 2019; R. M. Ortiz, Noren, Ortiz, & Talamantes, 2003; R. M. Ortiz, Wade, & Ortiz, 2001), without inducing muscle atrophy (Wright et al, 2020). The cellular mechanisms that drive tolerance to sustained glucocorticoid elevations in elephant seals, however, remain unexplored.…”

“…Recent work suggests that fasting-induced shifts in muscle metabolism stimulate pathways associated with preserving muscle mass in elephant seals (Wright et al, 2020), while earlier studies show that administration of exogenous ACTH upregulates catabolic genes in elephant seal skeletal muscle (Khudyakov, Champagne, Preeyanon, Ortiz, & Crocker, 2015; Khudyakov, Preeyanon, Champagne, Ortiz, & Crocker, 2015). Here, we generated a cellular model to study the mechanisms that drive tolerance to sustained glucocorticoid exposure in elephant seal muscle.…”