Metabolism research has made tremendous progress over the last several decades in establishing the adipocyte as a central rheostat in the regulation of systemic nutrient and energy homeostasis. Operating at multiple levels of control, the adipocyte communicates with organ systems to adjust gene expression, glucoregulatory hormone exocytosis, enzymatic reactions and nutrient flux to equilibrate the metabolic demands of a positive or negative energy balance. The identification of these mechanisms has great potential to identify novel targets for the treatment of diabetes and related metabolic disorders. Herein, we review the central role of the adipocyte in the maintenance of metabolic homeostasis highlighting three critical mediators: adiponectin, leptin, and fatty acids.

Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity.

ObjectiveShort sleep duration induces hormonal perturbations contributing to hyperphagia, insulin resistance, and obesity. The majority of these studies are conducted in young adults. This analysis in a large (n= 769) sample of postmenopausal women (median age 63 y) sought to 1) confirm that sleep duration and sleep quality are negatively correlated with circulating leptin concentrations and 2) to examine the relationship between self-reported sleep, dietary energy intake, and diet quality, as well as, investigate the role of leptin in these associations.Design and MethodsSleep duration/quality, insomnia, and dietary intake were determined via self-report. Blood samples were collected following an overnight fast to assess serum leptin concentration. All analyses were adjusted for total body fat mass.ResultsWomen reporting ≤6h sleep/night had lower serum leptin concentrations than those reporting ≥8h sleep (P= 0.04). Furthermore, those with ≤6h sleep/night reported higher dietary energy intake (p=0.01) and lower diet quality (P= 0.04) than the reference group (7h sleep/night). Women sleeping ≥8h also reported lower diet quality than the reference group (P= 0.02). Importantly, serum leptin did not confound these associations.ConclusionsThese results provide evidence that sleep duration is inversely associated with serum leptin and dietary energy intake in postmenopausal women.

Venom and its associated delivery systems have evolved in numerous animal groups ranging from jellyfishes to spiders, lizards, shrews, and the male platypus. Building off new data and previously published anatomical and molecular studies, we explore the evolution of and variation within venomous fishes. We show the results of the first multi-locus, ordinal-level phylogenetic analysis of cartilaginous (Chondrichthyes) and ray-finned (Actinopterygii) fishes that hypothesizes 18 independent evolutions of this specialization. Ancestral-states reconstruction indicates that among the 2386-2962 extant venomous fishes, envenomed structures have evolved four times in cartilaginous fishes, once in eels (Anguilliformes), once in catfishes (Siluriformes), and 12 times in spiny-rayed fishes (Acanthomorpha). From our anatomical studies and phylogenetic reconstruction, we show that dorsal spines are the most common envenomed structures (∼95% of venomous fish species and 15 independent evolutions). In addition to envenomed spines, fishes have also evolved venomous fangs (2% of venomous fish species, two independent evolutions), cleithral spines (2% of venomous fish species, one independent evolution), and opercular or subopercular spines (1% of venomous fish species, three independent evolutions).

Biofluorescence has recently been found to be widespread in marine fishes, including sharks. Catsharks, such as the Swell Shark (Cephaloscyllium ventriosum) from the eastern Pacific and the Chain Catshark (Scyliorhinus retifer) from the western Atlantic, are known to exhibit bright green fluorescence. We examined the spectral sensitivity and visual characteristics of these reclusive sharks, while also considering the fluorescent properties of their skin. Spectral absorbance of the photoreceptor cells in these sharks revealed the presence of a single visual pigment in each species. Cephaloscyllium ventriosum exhibited a maximum absorbance of 484 ± 3 nm and an absorbance range at half maximum (λ1/2max) of 440–540 nm, whereas for S. retifer maximum absorbance was 488 ± 3 nm with the same absorbance range. Using the photoreceptor properties derived here, a “shark eye” camera was designed and developed that yielded contrast information on areas where fluorescence is anatomically distributed on the shark, as seen from other sharks’ eyes of these two species. Phylogenetic investigations indicate that biofluorescence has evolved at least three times in cartilaginous fishes. The repeated evolution of biofluorescence in elasmobranchs, coupled with a visual adaptation to detect it; and evidence that biofluorescence creates greater luminosity contrast with the surrounding background, highlights the potential importance of biofluorescence in elasmobranch behavior and biology.

Objective Administration of glucagon (GCG) or GCG-containing co-agonists reduces body weight and increases energy expenditure. These actions appear to be transduced by multiple direct and indirect GCG receptor (GCGR)-dependent mechanisms. Although the canonical GCGR is expressed in brown adipose tissue (BAT) the importance of BAT GCGR activity for the physiological control of body weight, or the response to GCG agonism, has not been defined. Methods We studied the mechanisms linking GCG action to acute increases in oxygen consumption using wildtype (WT), Ucp1 −/− and Fgf21 −/− mice. The importance of basal GCGR expression within the Myf5 + domain for control of body weight, adiposity, glucose and lipid metabolism, food intake, and energy expenditure was examined in Gcgr BAT−/− mice housed at room temperature or 4 °C, fed a regular chow diet (RCD) or after a prolonged exposure to high fat diet (HFD). Results Acute GCG administration induced lipolysis and increased the expression of thermogenic genes in BAT cells, whereas knockdown of Gcgr reduced expression of genes related to thermogenesis. GCG increased energy expenditure (measured by oxygen consumption) both in vivo in WT mice and ex vivo in BAT and liver explants. GCG also increased acute energy expenditure in Ucp1 −/− mice, but these actions were partially blunted in Ffg21 −/− mice. However, acute GCG administration also robustly increased oxygen consumption in Gcgr BAT−/− mice. Moreover, body weight, glycemia, lipid metabolism, body temperature, food intake, activity, energy expenditure and adipose tissue gene expression profiles were normal in Gcgr BAT−/− mice, either on RCD or HFD, whether studied at room temperature, or chronically housed at 4 °C. Conclusions Exogenous GCG increases oxygen consumption in mice, also evident both in liver and BAT explants ex vivo , through UCP1-independent, FGF21-dependent pathways. Nevertheless, GCGR signaling within BAT is not physiologically essential for control of body weight, whole body energy expenditure, glucose homeostasis, or the adaptive metabolic response to cold or prolonged exposure to an energy dense diet.

Hyperglucagonemia, a hallmark in obesity and insulin resistance promotes hepatic glucose output, exacerbating hyperglycemia and thus predisposing to the development type 2 diabetes. As such, glucagon signaling is a key target for new therapeutics to manage insulin resistance. We evaluated glucagon homeostasis in lean and obese mice and people. In lean mice, fasting for 24 h caused a rise in glucagon. In contrast, a decrease in serum glucagon compared to baseline was observed in diet-induced obese mice between 8 and 24 h of fasting. Fasting decreased serum insulin in both lean and obese mice. Accordingly, the glucagon:insulin ratio was unaffected by fasting in obese mice but increased in lean mice. Re-feeding (2 h) restored hyperglucagonemia in obese mice. Pancreatic perfusion studies confirm that fasting (16 h) decreases pancreatic glucagon secretion in obese mice. Consistent with our findings in the mouse, a mixed meal increased serum glucagon and insulin concentrations in obese humans, both of which decreased with time after a meal. Consequently, fasting and re-feeding less robustly affected glucagon:insulin ratios in obese compared to lean participants. The glucoregulatory disturbance in obesity may be driven by inappropriate regulation of glucagon by fasting and a static glucagon:insulin ratio.

It has been proposed that Shc proteins may influence aging by regulating insulin signaling and energy metabolism. Evidence suggests that deletion of p66Shc could partially attenuate weight gain on a high fat diet by increasing energy expenditure. However, the impact of p66Shc on the metabolic response to calorie restriction (CR) has not been determined. Thus, we used indirect respiration calorimetry to determine the impact of CR on energy expenditure (EE) and substrate utilization (RQ) in 18mo p66Shc(−/−) and wild-type (WT) mice. Calorimetry measurements were completed at baseline and following 3d of 40% CR and 2mo of 26% CR. There was no difference (P>0.10) in EE and RQ between gentoypes, regardless of how EE data was normalized. Both p66Shc(−/−) and WT mice showed decreases (P<0.001) in EE normalized for body weight at 2mo of CR. However, the response to 3d of CR was different between genotypes with only the p66Shc(−/−) showing a decrease (P<0.001) in 24h EE expressed per mouse or normalized for body weight. The results indicate that p66Shc does not significantly influence EE in 18mo mice at baseline or 2mo of CR, although it may play a role in the EE response to very acute CR.