Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation

Mobilisation of blubber fatty acids of northern elephant seal pups (Mirounga angustirostris) during the post-weaning fast

Northern elephant seal pups were longitudinally sampled at Año Nuevo State Reserve during the post-weaning fast, in order to evaluate the changes of fatty acid (FA) profiles in serum as well as in the inner and outer layers of blubber. The major FAs of inner and outer blubber layers were broadly similar to those found in NES maternal milk previously measured, suggesting a direct deposit of dietary FAs in the blubber during the suckling period. The outer blubber layer contained more medium-chain monounsaturated FAs that contribute in keeping the fluidity of this tissue at cold temperatures. It was compensated by higher proportions of saturated FAs in the inner blubber layer. The FA signature of inner blubber, the layer that is mainly mobilised during energy deprivation, slightly differed from the signature of serum. There were greater proportions of medium-chain saturated FAs and ω-6 polyunsaturated FAs, and lower proportions of long-chain saturated FAs, medium-chain monounsaturated FAs and long-chain monounsaturated FAs in serum as compared to inner blubber. We also demonstrated that lipophilicity is the main factor governing the mobilisation of FAs from blubber. The least lipophilic FAs were preferentially hydrolysed from blubber, leading to an enrichment of the more lipophilic FAs in this tissue with the progression of the fast. The expression levels of HSL and ATGL, which are two enzymes involved in the lipolytic process, remained stable during the post-weaning fast. This suggests that the pups have developed the enzymatic mechanisms for an efficient lipolysis as soon as the first week of fast

Differential mobilization of fatty acids from blubber to blood during the post-weaning fast of northern elephant seals (Mirounga angustirostris)

The northern elephant seal (Mirounga angustirostris) is characterized by extended terrestrial fasting periods corresponding to breeding, lactation, moulting and post-weaning. During the post-weaning fast, pups mobilize primarily lipids from their large adipose tissue stores, to prevent protein catabolism and extend the developmental fast. In order to study the fatty acids (FAs) composition of different compartments throughout this period, serum samples and biopsies extending the full depth of the blubber layer were longitudinally obtained from 22 pups captured at 1-, 4-, 7- and 10-week post-weaning. Inner and outer blubber layers were analysed separately. Medium-chain monounsaturated FAs ( 1% by mass) represented more than 95% of the measured FAs in the 3 targeted compartments, the 2 main FAs being 18:1n-9 and 16:0. SFA and ω-3 PUFA were particularly well mobilized from inner blubber throughout the fast, followed by MC-MUFA and ω-6 PUFA. On the contrary, long-chain monounsaturated FAs (≥ 20C) tended to be conserved within the blubber. FAs with a high fractional mobilization are 20:5n-3, 16:0 and 16:1n-7. Their proportions decreased within inner blubber between early and late fast. On the contrary, the proportion of 20:1n-9 rose in inner blubber between early and late fast, as a result of its low mobilization rate from this compartment. The kinetics of FA mobilization were similar to that observed in other phocids as well as terrestrial mammals

WTO must ban harmful fisheries subsidies

Sustainably managed wild fisheries support food and nutritional security, livelihoods, and cultures (1). Harmful fisheries subsidies—government payments that incentivize overcapacity and lead to overfishing—undermine these benefits yet are increasing globally (2). World Trade Organization (WTO) members have a unique opportunity at their ministerial meeting in November to reach an agreement that eliminates harmful subsidies (3). We—a group of scientists spanning 46 countries and 6 continents—urge the WTO to make this commitment..