Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?

Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies.

Thermoregulatory Responses After Uphill Running While Wearing Enforcement Personnel Clothing

The choice of clothing for enforcement personnel is vital to ensure minimum physical interference and optimum freedom of movement. The clothing type and fibre composition are important factors that have strong influence on the activities of enforcement personnel. This study presents an evaluation of the thermoregulatory responses for two type of enforcement personnel clothing after uphill running with different material composition. Eight recreational trained respondents (age, 24.4 ± 2.3; height, 166.9 ± 3.3; body weight, 64.0 ± 5.8; BMI 23.0 ± 1.8) completed an 8 km run on a treadmill with 6% elevation wearing enforcement personnel clothing. Both clothing used in the trials were made of polyester/cotton (P50C50) and nylon/cotton (N20C80) material composition. The finding revealed that compared to P50C50 clothing, the N20C80 clothing does not have a good thermal balance. The loss of body mass did not vary significantly but the sweating rate differed significantly between trials (P = 0.008). The Rating of Perceived Exertion (RPE) of the participants was rated higher for N20C80 as compared to P50C50. The thermal sensation (P < 0.001), sweating sensation (P = 0.05), skin wetness (P = 0.007), clothing comfort (P < 0.01) and clothing humidity (P = 0.001) were significantly greater with N20C80 compared to P50C50 during exercise. The P50C50 clothing was more convenient to wear for the uphill running during the exercise. This study suggested that P50C50 would provide a better thermoregulatory response to regulate the thermal equilibrium between human skin and the environment.

Thermoregulatory response of Yankasa sheep with distinct thick-coarse and shortslick hair types during hot-dry season in tropical Savannah

The skin has the closest contact with the environment and, thus, the role of coat in the adaptation to the changing environmental conditions cannot be over emphasised. The study was aimed at comparing the thermoregulatory response of Yankasa rams with distinct thick coarse and short-slick hair types at the peak of the hot-dry season in tropical Guinea Savannah. A total of 10 Yankasa rams with thick-coarse (n=5) and short-slick (n=5) hair types, balanced for age and body condition score were used. The meteorological and thermoregulatory parameters were measured four times at 2 days interval at 9:00, 13:00 and 17:00 h. In the afternoon, the temperature humidity index and ambient temperature were higher than the thermoneutral zone for sheep. Yankasa sheep with thick-coarse hair had higher (P < 0.05) hair length than those with short-slick hair type. Respiratory rate at all hours, body surface temperature in the morning hours, eye and inter-digital surface temperature in the afternoon hours were lower in thick-coarse hair than short-slick hair sheep. Significant rise (P < 0.05) in respiratory rate, skin and rectal temperatures from morning to afternoon hours were observed in both hair types. Subsequently, in the evening hours, the rectal temperature in the thick-coarse hair sheep returned to values comparable to those of the morning hours; while the values in short-slick hair sheep remained higher (P <0.05) than that of the morning hours. It was concluded that Yankasa sheep with thick-coarse hair type had lower thermoregulatory demand to maintain homeostasis in the afternoon hours, and cooled faster in the evening hours relative to their short-slick hair type counterpart during the hot-dry season in the tropical Savannah. La peau a le contact le plus facile avec l'environnement et, par conséquent, le rôle du pelage dans l'adaptation aux conditions environnementales changeantes ne peut pas être trop souligné. L'étude visait à comparer la réponse thermorégulatrice des béliers yankasa avec des types distincts de cheveux épais-grossiers et courts au plus fort de la saison chaude et sèche dans la savane tropicale de Guinée. Un total de 10 béliers Yankasa avec des types de cheveux épais-grossiers (n=5) et short-slick (n=5), équilibrés pour l'âge et le score d'état corporel ont été utilisés. Les paramètres météorologiques et thermorégulateurs ont été mesurés quatre fois à intervalles de 2 jours à 9 h, 13 h et 17 h. Dans l'après-midi, l'indice d'humidité de la température et la température ambiante étaient plus élevés que la zone thermonéutrale pour les moutons. Les moutons Yankasa aux cheveux épais et grossiers avaient une longueur de cheveux plus élevée (P < 0.05) que ceux de type cheveux courts. La fréquence respiratoire à toute heure, la température de surface du corps le matin, la température des yeux et de la surface inter-numérique dans les heures de l'après-midi étaient plus faibles dans les cheveux épais-grossiers que les moutons cheveux courts lisses. Des hausses significatives (P < 0.05) des températures respiratoires, cutanées et rectales du matin à l'après-midi ont été observées dans les deux types de cheveux. Par la suite, le soir, la température rectale chez les moutons aux cheveux épais-grossiers est revenue à des valeurs comparables à celles des heures du matin; tandis que les valeurs chez les moutons à poils courts sont restées plus élevées (P < 0.05) que celles des heures du matin. Il a été conclu que les moutons Yankasa de type cheveux épais-grossiers avaient une demande thermorégulatrice plus faible pour maintenir l'homéostasie dans les heures de l'après-midi, et refroidi plus rapidement dans les heures du soir par rapport à leur homologue de type cheveux courts lisses pendant la saison chaude-sèche dans la savane tropicale

Impact of ambient temperature on inflammation-induced encephalopathy in endotoxemic mice—role of phosphoinositide 3-kinase gamma

Background Sepsis-associated encephalopathy (SAE) is an early and frequent event of infection-induced systemic inflammatory response syndrome. Phosphoinositide 3-kinase γ (PI3Kγ) is linked to neuroinflammation and inflammation-related microglial activity. In homeotherms, variations in ambient temperature (Ta) outside the thermoneutral zone lead to thermoregulatory responses, mainly driven by a gradually increasing sympathetic activity, and may affect disease severity. We hypothesized that thermoregulatory response to hypothermia (reduced Ta) aggravates SAE in PI3Kγ-dependent manner. Methods Experiments were performed in wild-type, PI3Kγ knockout, and PI3Kγ kinase-dead mice, which were kept at neutral (30 ± 0.5 °C) or moderately lowered (26 ± 0.5 °C) Ta. Mice were exposed to lipopolysaccharide (LPS, 10 μg/g, from Escherichia coli serotype 055:B5, single intraperitoneal injection)—evoked systemic inflammatory response (SIR) and monitored 24 h for thermoregulatory response and blood–brain barrier integrity. Primary microglial cells and brain tissue derived from treated mice were analyzed for inflammatory responses and related cell functions. Comparisons between groups were made with one-way or two-way analysis of variance, as appropriate. Post hoc comparisons were made with the Holm–Sidak test or t tests with Bonferroni’s correction for adjustments of multiple comparisons. Data not following normal distribution was tested with Kruskal-Wallis test followed by Dunn’s multiple comparisons test. Results We show that a moderate reduction of ambient temperature triggers enhanced hypothermia of mice undergoing LPS-induced systemic inflammation by aggravated SAE. PI3Kγ deficiency enhances blood–brain barrier injury and upregulation of matrix metalloproteinases (MMPs) as well as an impaired microglial phagocytic activity. Conclusions Thermoregulatory adaptation in response to ambient temperatures below the thermoneutral range exacerbates LPS-induced blood–brain barrier injury and neuroinflammation. PI3Kγ serves a protective role in suppressing release of MMPs, maintaining microglial motility and reinforcing phagocytosis leading to improved brain tissue integrity. Thus, preclinical research targeting severe brain inflammation responses is seriously biased when basic physiological prerequisites of mammal species such as preferred ambient temperature are ignored.

Impact of Ambient Temperature on Inflammation-induced Encephalopathy in Endotoxemic Mice—Role of Phosphoinositide 3-Kinase Gamma

Background: Sepsis-associated encephalopathy (SAE) is an early and frequent event of infection-induced systemic inflammatory response syndrome. Phosphoinositide 3-kinase γ (PI3Kγ) is linked to neuroinflammation and inflammation-related microglial activity. In homeotherms, variations in ambient temperature (Ta) outside the thermoneutral zone lead to thermoregulatory responses, mainly driven by a gradually increasing sympathetic activity, and may affect disease severity. We hypothesized that thermoregulatory response to hypothermia (reduced Ta) aggravates SAE in PI3Kγ-dependent manner.Methods: Experiments were performed in wild-type, PI3Kγ knockout, and PI3Kγ kinase-dead mice, which were kept at neutral (30±0.5°C) or moderately lowered (26±0.5°C) Ta. Mice were exposed to lipopolysaccharide (LPS, 10 μg/g, from Escherichia coli serotype 055:B5, single intraperitoneal injection) - evoked systemic inflammatory response (SIR) and monitored 24 hours for thermoregulatory response and blood–brain barrier integrity. Primary microglial cells and brain tissue derived from treated mice were analyzed for inflammatory responses and related cell functions. Comparisons between groups were made with one-way or two-way analysis of variance, as appropriate. Post hoc comparisons were made with the Holm–Sidak test or t-tests with Bonferroni’s correction for adjustments of multiple comparisons. Data not following normal distribution was tested with Kruskal-Wallis test followed by Dunn’s multiple comparisons test.Results: We show that a moderate reduction of ambient temperature triggers enhanced hypothermia of mice undergoing LPS-induced systemic inflammation by aggravated SAE. PI3Kγ deficiency enhances blood–brain barrier injury and upregulation of matrix metalloproteinases (MMPs) as well as an impaired microglial phagocytic activity.Conclusions: Thermoregulatory adaptation in response to ambient temperatures below the thermoneutral range exacerbates LPS-induced blood–brain barrier injury and neuroinflammation. PI3Kγ serves a protective role in suppressing release of MMPs, maintaining microglial motility and reinforcing phagocytosis leading to improved brain tissue integrity. Thus, preclinical research targeting severe brain inflammation responses is seriously biased when basic physiological prerequisites of mammal species such as preferred ambient temperature are ignored.