Seasonal regulation of the growth hormone-insulin-like growth factor-I axis in the American black bear (Ursus americanus)

Abstract

The American black bear maintains lean body mass for months without food during winter denning. We asked whether changes in the growth hormone/insulin-like growth factor-I (GH-IGF-I) axis may contribute to this remarkable adaptation to starvation. Serum IGF-I levels were measured by radioimmunoassay, and IGF-binding proteins (IGFBPs) were analyzed by ligand blotting. Initial studies in bears living in the wild showed that IGF-I levels are highest in summer and lowest in early winter denning. Detailed studies in captive bears showed that IGF-I levels decline in autumn when bears are hyperphagic, continue to decline in early denning, and later rise above predenning levels despite continued starvation in the den. IGFBP-2 increased and IGFBP-3 decreased in early denning, and these changes were also reversed in later denning. Treatment with GH (0.1 mg·kg−1·day−1 × 6 days) during early denning increased serum levels of IGF-I and IGFBP-3 and lowered levels of IGFBP-2, indicating that denning bears remain responsive to GH. GH treatment lowered blood urea nitrogen levels, reflecting effects on protein metabolism. GH also accelerated weight loss and markedly increased serum levels of free fatty acids and β-hydroxybutyrate, resulting in a ketoacidosis (bicarbonate decreased to 15 meq/l), which was reversed when GH was withdrawn. These results demonstrate seasonal regulation of GH/IGF-I axis activity in black bears. Diminished GH activity may promote fat storage in autumn in preparation for denning and prevent excessive mobilization and premature exhaustion of fat stores in early denning, whereas restoration of GH/IGF activity in later denning may prepare the bear for normal activity outside the den.

Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

“…In late-fasted seals, FFAs and the endocannabinoids, AEA and OEA, decreased during the first 60 min of insulin infusion followed by a return to baseline values. In hibernating bears, the growth hormone-induced increase in insulin was associated with nearly a fourfold increase in FFA 7 days post-infusion suggestive of increased lipolysis (Blumenthal et al 2011). The corresponding reductions in AEA and OEA are consistent with previous data demonstrating that endocannabinoid and N-acylethanolamides reflect changes in FFA concentrations (Joosten et al 2010).…”

“…On the contrary, 3-hydroxybutyric acid decreased during the first 60 min of insulin infusion and remained suppressed suggesting that under normal conditions insulin promotes the complete metabolism of ketones so that they do not accumulate. In contrast, the growth hormone-induced increase in insulin stimulated over a 6-fold increase in plasma β-hydroxy butyrate in hibernating bears (Blumenthal et al 2011). The differential responses compared to hibernating bears most likely reflect differences in energetic demands between the two animals as hibernating bears are hypothermic and metabolically quiescent while fasting seal pups are metabolically active and normothermic.…”

New lipid‐producing, cold‐tolerant yellow‐green alga isolated from the rocky mountains of colorado

“…If lipids were significantly catabolized, we would have seen pits but no pits were seen. The relative fluorescence level of Nile Red and Bodipy dyes can be used to estimate lipid levels but previous studies have found that fluorescence levels do not necessarily correlate well with the fat levels detected by GC‐MS …”

“…If lipids were significantly catabolized, we would have seen pits but no pits were seen. The relative fluorescence level of Nile Red and Bodipy dyes can be used to estimate lipid levels but previous studies have found that fluorescence levels do not necessarily correlate well with the fat levels detected by GC-MS. 15,16 No environmental treatment was shown to improve lipid accumulation, including high light, nitrogen starvation, bubbling CO 2 -containing air into liquid cultures, and changing the pH of the media. About 96 h treatments of heat stress (4-22 C), dark stress, or both heat and dark stresses applied concurrently changed fatty acid composition ( Table 2).…”

Synergistic and threshold effects of GH1 and GHR promoter size variation on body growth and fat accrual in young Nelore (Bos indicus) bulls

“…A classical example is the seasonal regulation of the GH1/IGF1 axis in bears, in which diminished GH1/IGF1 activity by overeating promotes fat storage in preparation for winter denning (Blumenthal et al, 2011). Low GH1 secretion is associated with features of the metabolic syndrome, in particular increased visceral body fat and decreased lean body mass.…”