The hormones ghrelin and leptin act via the lateral hypothalamic area (LHA) to modify energy balance, but the underlying neural mechanisms remain unclear. We investigated how leptin and ghrelin engage LHA neurons to modify energy balance behaviors and whether there is any crosstalk between leptin and ghrelin-responsive circuits. We demonstrate that ghrelin activates LHA neurons expressing hypocretin/orexin (OX) to increase food intake. Leptin mediates anorectic actions via separate neurons expressing the long form of the leptin receptor (LepRb), many of which coexpress the neuropeptide neurotensin (Nts); we refer to these as NtsLepRb neurons. Because NtsLepRb neurons inhibit OX neurons, we hypothesized that disruption of the NtsLepRb neuronal circuit would impair both NtsLepRb and OX neurons from responding to their respective hormonal cues, thus compromising adaptive energy balance. Indeed, mice with developmental deletion of LepRb specifically from NtsLepRb neurons exhibit blunted adaptive responses to leptin and ghrelin that discoordinate the mesolimbic dopamine system and ingestive and locomotor behaviors, leading to weight gain. Collectively, these data reveal a crucial role for LepRb in the proper formation of LHA circuits, and that NtsLepRb neurons are important neuronal hubs within the LHA for hormone-mediated control of ingestive and locomotor behaviors.
Exercise or work in hot environments increases susceptibility to exertional heat illnesses such as exertional heat stroke (EHS). EHS occurs when body heat gain exceeds body heat dissipation, resulting in rapid body heat storage and potentially life-threatening consequences. EHS poses a dangerous threat for athletes, agriculture workers, and military personnel, as they are often exposed to hot environmental conditions that restrict body heat loss or contribute to body heat gain. Currently, there is limited guidance on return to activity (RTA) after an episode of EHS. While examining biomarkers in the blood is thought to be beneficial for determining RTA, they are not sensitive or specific enough to be a final determining factor as organ damage may persist despite blood biomarkers returning to baseline levels. As such, additional assessment tests to more accurately determine RTA are desired. One method used for determining RTA is the heat tolerance test (HTT, 120 minutes treadmill walking; 40°C, 40% relative humidity). Unfortunately, the HTT provides even less information about EHS recovery since it offers no test sensitivity or specificity even after years of implementation. We provide an overview of the HTT and the controversy of this test with respect to assessment criteria, applicability to tasks involving high metabolic workloads, and the lack of follow-up analyses to determine its accuracy for determining recovery in order to diminish the likelihood of a second EHS occurrence.
Introduction Precipitating factors that contribute to the severity of exertional heat stroke (EHS) are unclear. The purpose of this study was to determine the effect of prior illness (PI) on EHS severity. Methods We performed a retrospective clinical record review of 179 documented cases of EHS at the Marine Corps Base in Quantico, Virginia. Results Approximately 30% of EHS cases had a medically documented PI. Anthropometrics (height, weight, body mass index) and commonly associated risk factors for EHS (age, number of days in training, wet bulb globe temperature, sleep patterns) did not differ between PI and no illness (NI) groups. PI patients presented with higher maximal rectal core temperatures (40.6 ± 1.0°C vs. 40.3 ± 1.2°C; P = 0.0419), and elevated pulse rates (118.1 ± 16.7 bpm vs. 110.5 ± 24.2 bpm; P = 0.0397). At the point of care, biomarker values were similar between PI and NI groups, with the exception of a trend toward elevated monocytes in those with PI (7.9 ± 2.9% vs 6.7± 2.7%; P = 0.0521). Rate and duration of cooling were similar between PI and NI patients. Conclusion This study indicates that PI has a minimal effect on the patient presentation, severity and treatment outcome of EHS. The results of this study have important implications for military, civilian, and occupational populations who are at risk for EHS.
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