Mice are commonly housed at room temperatures below their thermoneutral zone meaning they are exposed to chronic thermal stress. r Endurance exercise induces browning and mitochondrial biogenesis in white adipose tissue of rodents, but there are conflicting reports of this phenomenon in humans. r We hypothesized that the ambient room temperature at which mice are housed could partially explain these discrepant reports between humans and rodents. r We housed mice at room temperature or thermoneutrality and studied their physiological responses to acute and chronic exercise. We found that thermoneutral housing altered running behaviour and glucose homeostasis, and further, that exercise-induced markers of mitochondrial biogenesis and the browning of white adipose tissue were reduced in mice housed at thermoneutrality.

support-information-section). OLZ Glucagon Blood sugar Ketogenic diet Fasting α cell Centrally mediated effects of OLZ on glucagon Direct effects of OLZ on the pancreasAbstract Antipsychotic (AP) medications, such as olanzapine (OLZ), are used in the treatment of schizophrenia and a growing number of 'off-label' conditions. A single dose of OLZ causes robust increases in blood glucose within minutes of treatment. The purpose of the current study was to investigate whether interventions that increase circulating ketone bodies (fasting, β-hydroxybutyrate (βHB), ketone esters or a ketogenic diet (KD)) would be sufficient to protect against the acute metabolic side effects of OLZ. We demonstrate that fasting or the short-term consumption of a KD Hesham Shamshoum joined Dr David Wright's laboratory to pursue his Doctorate in the

Various endocrine factors contribute to cold‐induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole‐body glucagon receptor knockout (Gcgr−/−) mice and their wild‐type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3‐adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr−/− mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr−/− mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone‐sensitive lipase were attenuated in iWAT of Gcgr−/− mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold‐induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.—Townsend, L. K., Medak, K. D., Knuth, C. M., Peppier, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning. FASEB J. 33, 4824–4835 (2019). http://www.f asebj.org

Historically, interleukin-6 (IL-6) was considered a proinflammatory cytokine contributing to the development of obesity-associated insulin resistance (1-3). However, accumulating evidence now suggests that IL-6 may contribute to the maintenance of normal systemic glucose metabolism (4-8) and that the increased circulating IL-6 concentrations during obesity may actually be an adaptive mechanism to resist obesity-associated glucose intolerance (9). One of the first reports to challenge the dogma of IL-6 as a detrimental cytokine showed that IL-6-deficient mice develop late-onset obesity and systemic glucose intolerance (10). Subsequently, it was shown that a single high-dose injection of IL-6 (400 ng) improved glucose tolerance in lean, high-fat diet (HFD)-induced obese mice, streptozytocin-induced diabetic mice, ob/ob mice, and db/db mice (7). Moreover, chronic antagonism of IL-6 worsens glucose metabolism in db/db mice (7). Together, these data strongly support a more favorable role for IL-6 in the maintenance of systemic glucose homeostasis. IL-6 may achieve some of its metabolic benefits via classical signaling in the liver, the tissue with one of the greatest concentrations of IL-6 receptors in the body, at least in mice and rats (8). This might explain why IL-6-deficient mice develop hepatic steatosis, inflammation, and insulin resistance, even when on a chow diet (11). Moreover, when the IL-6 receptor was genetically ablated specifically in the liver, mice developed hepatic inflammation, systemic glucose intolerance,

Increased serial sarcomere number (SSN) has been observed in rats following downhill running training due to the emphasis on active lengthening contractions; however, little is known about the influence on dynamic contractile function. Therefore, we employed 4 weeks of weighted downhill running training in rats, then assessed soleus SSN and work loop performance. We hypothesised trained rats would produce greater net work output during work loops due to a greater SSN. Thirty-one Sprague-Dawley rats were assigned to a training or sedentary control group. Weight was added during downhill running via a custom-made vest, progressing from 5–15% body mass. Following sacrifice, the soleus was dissected, and a force-length relationship was constructed. Work loops (cyclic muscle length changes) were then performed about optimal muscle length (LO) at 1.5–3-Hz cycle frequencies and 1–7-mm length changes. Muscles were then fixed in formalin at LO. Fascicle lengths and sarcomere lengths were measured to calculate SSN. Intramuscular collagen content and crosslinking were quantified via a hydroxyproline content and pepsin-solubility assay. Trained rats had longer fascicle lengths (+13%), greater SSN (+8%), and a less steep passive force-length curve than controls (P<0.05). There were no differences in collagen parameters (P>0.05). Net work output was greater (+78–209%) in trained than control rats for the 1.5-Hz work loops at 1 and 3-mm length changes (P<0.05), however, net work output was more related to maximum specific force (R2=0.17-0.48, P<0.05) than SSN (R2=0.03-0.07, P=0.17-0.86). Therefore, contrary to our hypothesis, training-induced sarcomerogenesis likely contributed little to the improvements in work loop performance. This article has an associated First Person interview with the first author of the paper.