Human white-fat thermogenesis: Experimental and meta-analytic findings

Abstract

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 (T env) and exercise. Low T env 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 T env and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low T env 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 protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low T env on human WAT thermogenic activity (p > 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p > 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and metaanalytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUV max , demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity.

Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

“…Upon its discovery, irisin has been a subject of intense investigation [15]. Since irisin is an exercise-induced hormone [6] and passes a signal to AT, it is important to identify the molecular mechanisms that mediate its effects.…”

“…Irisin is an adipo-myokine secreted mainly by skeletal muscle and by AT, after the proteolytic cleavage of fibronectin type III domaincontaining protein 5 (FNDC5) [6]. Physical activity induces the expression of irisin through the activation of the transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ), the coactivator-1α (PGC-1α) and of FNDC5 [15,23]. These pathways are involved in the browning of WAT [50].…”

Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

“…Both in vivo and in vitro models are necessary to effectively understand the mechanisms involved in the browning process. This is demonstrated by the controversy observed between in vivo human and animal studies regarding exercise-induced adipose tissue browning, which is likely caused by a variability in the exercise protocols used and different methods of browning detection [23]. Moreover, exercise exerts many whole-body adaptations, which are difficult to study separately through in vivo studies.…”

“…In contrast, other studies using similar exercise protocols reported that exercise upregulated the browning process, but without any positive effects on the metabolism of the volunteers [16]. This stark controversy between animal and human studies with respect to the impact of exercise on the browning process has been demonstrated in a recent series of meta-analyses [23] and has been attributed to (i) heterogeneity of white adipose tissue depots [17], (ii) the variability in sample collection in animals and, mainly, humans [17,24], and (iii) a host of external factors (e.g., nutrition, environmental temperature, other stressors) that may interfere with the effect of exercise on the browning process [6,23]. Therefore, there is a need for in vitro experiments aiming to identify the factors and the procedures which can induce browning of white lipocytes under the effect of exercise.…”

Effects of Nutrition/Diet on Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis

“…Indeed, body mass index (BMI) [15], age [16] and fat mass [1] are inversely associated with BAT activity. This is not surprising, since BMI and fat mass are inversely associated with white adipose tissue thermogenic activity in humans [17].…”