White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (Tenv) and exercise. Low Tenv may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of Tenv and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low Tenv and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocoTomography and Computed Tomography; REE Resting energy expenditure; 18F-FDG F18 fludeoxyglucose; VO2peakPeak oxygen consumption; 1RM One repetition maximum; SUVmax Maximum standardized uptake value; Std Standardized mean difference.A cardiovascular requirement to facilitate thermal homeostasis may partly contribute to the elevated heart rate during eccentric cycling. This study compared the body temperature response to a bout of eccentric (ECC) and concentric (CON) cycling to account for the difference in heart rate. Eight (N = 8) aerobically trained males (age 35 y [SD 8], peak oxygen consumption 3.82 L.min-1 [SD 0.79]) completed an ECC cycling trial (60% PPO) followed by an oxygen consumption/duration matched CON trial (30 ∘ C , 35% RH) on a separate day. Trial termination was determined as an elevation in aural temperature, a surrogate of deep body temperature, by +0.5 ∘ C during ECC. INCB024360 Mean skin (8-sites) and body temperature (weighting of 8020 for auditory canal and mean skin temperature) were calculated. Matching the oxygen consumption between the trials increased external work during ECC cycling (CON 71 [SD 14] ECC 194 [SD 38] W, p less then 0.05) and elevated aural temperature (+0.5 ∘ C ) by 20 min 32 s [SD 9 min 19 s] in that trial. The peak rate of rise in aural temperature was significantly greater in ECC (CON 0.012 [SD 0.007] ECC 0.031 [SD 0.002] oC.s-1, p less then 0.05). Aural, mean skin and body temperature were significantly higher during the ECC trial (p less then 0.05) and this was accompanied by elevated mean heart rate (CON 103 [SD 14] ECC 118 [SD 12] b.min-1, p less then 0.05) and thermal discomfort (p less then 0.05). Moderate load eccentric cycling imposes an elevated thermal strain when compared to concentric cycling. This requirement for dissipating heat, in part, explains the elevated heart rate during eccentric cycling.We investigated whether and how multiple sclerosis (MS) alters thresholds for perceiving increases and decreases in local skin temperature, as well as the sensitivity to progressively greater temperature stimuli, amongst heat-sensitive people with MS. Eleven MS patients (5 M/6 F; 51.1 ± 8.6 y, EDSS 5.7 ± 1.9) and 11 healthy controls (CTR; 7 M/4 F; 50.3 ± 9.0 y) performed warm and cold threshold tests on a hairy skin site, on both sides of the body. They also underwent a thermosensitivity test where they rated (visual analogue scale) perceived magnitude of 4 local skin stimuli (i.e. 22, 26, 34, 38°C). Individual thresholds and slopes of linear regression for thermosensitivity were z-transformed for each MS patient, and used to determine individual thermosensory abnormalities. When considering both threshold and thermosensitivity, six out of our 11 heat-sensitive patients (54.5%) exhibited skin thermosensory abnormalities. Those abnormalities varied amongst patients in terms of type (threshold vs. thermosensitivity), quality (warm vs. cold), location (left vs. right side of the body) and extent. Each of those six patients presented unique thermosensory profiles. While some patients experienced thermosensory loss in both thresholds and sensitivity and on both sides of the body, others experienced cold thermosensory loss on one side of the body only. The observed individual variability in thermosensory function among heat-sensitive MS patients highlight the need for a patient-centered approach to assessing thermosensory dysfunction and its potential implications for heat stress vulnerability in this patient group.In studies of human thermoregulation, ingestible temperature pills are being increasingly used as a convenient alternative to more clinically relevant indices of deep-body (core) temperature (e.g., rectal temperature). It remains unclear whether the time between pill ingestion and the measurement period influences the validity of telemetry pills as a surrogate index of core temperature. We therefore assessed the influence of pill ingestion timing on the agreement between rectal temperature (criterion method) and ingestible pill temperature during exercise-heat stress. To achieve this, nine young men (21-31 years) completed two trials involving 15-min rest, 90-min exercise at an average metabolic heat production of 200 W/m2 (~40% peak oxygen consumption), and 45-min recovery. Core temperature was measured throughout using rectal temperature and four telemetric temperature pills (VitalSense®) ingested 12, 6, 3 and 1 h(s) prior to the start of each trial. Data from the two trials were combined and averaged over the final 10-min of rest, exercise, and recovery for analysis. Our primary finding was that the mean squared difference between rectal temperature and each pill did not differ significantly across ingestion times during rest, exercise or recovery (p = 0.056), with those errors ranging from 0.1-0.2°C, 0.2-0.2°C, 0.1-0.2°C, and 0.1-0.2°C for the pills ingested 12, 6, 3, and 1 h(s) before data collection, respectively. While there is a need for larger confirmatory studies, our findings indicate that pill ingestion timing does not significantly influence the validity of telemetry pill temperature as an index of core temperature.