Maternal antibodies directed to pre-F, followed by antibodies directed to G, can modulate RSV disease severity in young infants.

Non-shivering thermogenesis can promote negative energy balance and weight loss. In this study, we identify a contextual stimulus that induces rapid and robust thermogenesis in skeletal muscle. Rats exposed to the odor of a natural predator (ferret odor) show elevated skeletal muscle temperatures detectable as quickly as 2 min after exposure, reaching maximum thermogenesis of >1.5 °C at 10-15 min. Mice exhibit a similar thermogenic response to the same odor. Ferret odor induces a significantly larger and qualitatively different response than do novel or aversive odors, fox odor, or moderate restraint stress. Exposure to predator odor increases energy expenditure, and both the thermogenic and energetic effects persist when physical activity levels are controlled. Predator odor-induced muscle thermogenesis is subject to associative learning as exposure to a conditioned stimulus provokes a rise in muscle temperature in the absence of the odor. The ability of predator odor to induce thermogenesis is predominately controlled by sympathetic nervous system activation of β-adrenergic receptors, as unilateral sympathetic lumbar denervation and a peripherally acting β-adrenergic antagonist significantly inhibit predator odor-induced muscle thermogenesis. The potential survival value of predator odor-induced changes in muscle physiology is reflected in an enhanced resistance to running fatigue. Lastly, predator odor-induced muscle thermogenesis imparts a meaningful impact on energy expenditure as daily predator odor exposure significantly enhances weight loss with mild calorie restriction. This evidence signifies contextually provoked, centrally mediated muscle thermogenesis that meaningfully impacts energy balance.

We have previously identified predator odor as a potent stimulus activating thermogenesis in skeletal muscle in rats. As this may prove relevant for energy balance and weight loss, the current study investigated whether skeletal muscle thermogenesis was altered with negative energy balance, obesity propensity seen in association with low intrinsic aerobic fitness, and monogenic obesity. First, weight loss subsequent to 3 wk of 50% calorie restriction suppressed the muscle thermogenic response to predator odor. Next, we compared rats bred based on artificial selection for intrinsic aerobic fitness – high- and low-capacity runners (HCR, LCR) – that display robust leanness and obesity propensity, respectively. Aerobically fit HCR showed enhanced predator odor-induced muscle thermogenesis relative to the less-fit LCR. This contrasted with the profound monogenic obesity displayed by rats homozygous for a loss of function mutation in Melanocortin 4 receptor ( Mc4r K3a,4X/K314X rats), which showed no discernable deficit in thermogenesis. Taken together, these data imply that body size or obesity per se are not associated with deficient muscle thermogenesis. Rather, the physiological phenotype associated with polygenic obesity propensity may encompass pleiotropic mechanisms in the thermogenic pathway. Adaptive thermogenesis associated with weight loss also likely alters muscle thermogenic mechanisms.

Obesity is a worldwide trend that is cause for concern due to its detrimental effects on numerous health factors and increased risk of mortality. The propensity for obesity, although influenced by diet, is also worsened by sedentary lifestyle. Indeed, individuals' daily activity levels and activity energy expenditure predict weight gain and obesity. Increased energy expenditure, whether deliberate or spontaneous, is associated with leanness and reduced risk for obesity. With respect to increasing energy expenditure through thermogenesis, previous investigation has focused largely on browning of white adipose and brown adipose tissue thermogenesis, with much less attention paid to mechanisms mediating thermogenesis in skeletal muscle. Here, we investigated the effects of contextually induced muscle thermogenesis in rats through exposure to predator odor in rats. We hypothesize that thermogenesis in skeletal muscle is mediated by the sympathetic nervous system (SNS), specifically through activation of muscle β‐adrenergic receptors. To test this, we examined the effects of nadolol, a peripherally acting β‐adrenergic antagonist, on predator odor‐induced thermogenesis. IPTT‐300 transponders from Bio Medic Data Systems were surgically implanted in the left and right gastrocnemius muscles of male rats (N=13). Rats were exposed to each of four conditions (2×2): nadolol or saline vehicle, each with and without predator odor (1.5″×2″ towel with ferret odor) or control stimulus; muscle temperatures were measured over 120 minutes. Predator odor significantly induced muscle thermogenesis in vehicle‐treated animals. The mixed β‐adrenergic antagonist nadolol significantly reduced predator odor‐induced thermogenesis. This demonstrates that predator odor‐induced skeletal muscle thermogenesis is mediated, at least in part, by β‐adrenergic receptor activation, likely stemming from sympathetic nerve activation. Our previous work has demonstrated that this thermogenic induction is accompanied by enhanced energy expenditure. With the focus on muscle, rather than adipose thermogenesis, we establish a pathway that expands the understanding of energy balance, its mechanisms, and possible treatments. Going forward, induction of muscle thermogenesis may be applied to the treatment of obesity.Support or Funding InformationNIH NIDDK R15‐DK‐097644 and R15‐DK‐108668 to CMNThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.