{"doi":"10.1113/jp284459","title":"Turn up and burn up: aerobic exercise training as a strategy to preserve non‐shivering thermogenesis on an obesogenic diet","abstract":"With positive energy balance, adipose tissue hypertrophies and contributes to negative health outcomes, such as metabolic syndrome. However, white and brown adipose tissue (BAT) have divergent effects on health. Excessive white adipose tissue is associated with negative health outcomes, whereas BAT contributes to energy dissipation and attenuated weight gain. Specifically, BAT contains uncoupling protein-1 (UCP-1), which, when triggered by the release of noradrenaline, uncouples ATP synthase, causing hydrogen ions to leak across the inner mitochondrial membrane, resulting in non-shivering thermogenesis (Da Eira et al., 2023). The existing literature suggests that non-shivering thermogenesis through BAT is insufficient to prevent weight gain (i.e. the present obesity epidemic) or is even suppressed in the context of obesity. For example, compared with lean young males, young males with obesity have <40% of the activation of BAT after cold exposure, despite having approximately twice the volume of BAT (Leitner et al., 2017). Therefore, in a recent article in The Journal of Physiology, Da Eira et al. (2023) sought to examine mechanistic changes leading to impaired diet-induced thermogenesis in BAT in the context of an obesogenic diet. Da Eira et al. (2023) fed male albino Wistar rats either standard chow (SC; Control) or high-fat sucrose-enriched (HFS) diet ad libitum for 8 weeks. The rats were anaesthetized after the feeding trials, and tissues were harvested for the experiments of the present study. The research team measured glucose uptake, lactate production and tissue morphology of the adipose tissue. Transcription and translation of specific proteins of interest [i.e. peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), carnitine palmitoyltransferase 1β (CPT-1β), UCP-1, CD36 and lipoprotein lipase (LPL)] were measured using quantitative PCRs and western blotting. Consistent with previous human data (Leitner et al., 2017), HFS-fed rats gained more weight, exhibited greater adiposity (subcutaneous inguinal and epididymal fat pads) and greater mass of BAT (interscapular and aortic BAT). Within BAT, there was increased expression of the thermogenic proteins PGC-1α (an oxidative phosphorylation protein), CPT-1β (fatty acid transporter in skeletal muscle mitochondria), in response to the HFS diet. Increased expression of thermogenic proteins indicates greater potential for thermogenesis; however, uncoupled glucose and fatty acid oxidation were reduced after the HFS diet. Exposure to the HFS diet also resulted in increased glucose uptake transporter 1 (GLUT1) expression and increased basal and insulin-stimulated glucose uptake in BAT adipocytes. Additionally, several mechanistic changes indicating greater potential triacylglycerol synthesis occurred after the HFS diet. For example, glycerol was incorporated into lipids and palmitate into triacylglycerol at significantly greater rates. Upregulation of CD36 (a cell membrane fatty acid transporter) and LPL (which cleaves esterified fatty acids from chylomicrons circulating in the bloodstream) indicated increased potential for fatty acid absorption into cells. Furthermore, glycerol release (a proxy measure of triacylglycerol lipolysis) and adipose triacylglycerol lipase (the first enzymatic step of lipolysis) were decreased, while Phosphoenolpyruvate Carboxykinase (PEPCK; converts pyruvate into phosphorylated glycerol) and glycerol kinase (which phosphorylates glycerol) were increased after the HFS diet. Collectively, these data suggest that the HFS diet resulted in BAT downregulating lipolysis and upregulating enzymes responsible for the esterification of triacylglycerol, indicating that BAT adipocytes from HFS diet-fed rats are storing fatty acids as triacylglycerol rather than oxidizing fatty acids for thermogenesis. Interestingly, BAT β3-adrenergic receptor expression was upregulated in the HFS diet-fed rats. In isolation, this finding would suggest that noradrena","journal":"The Journal of Physiology","year":2023,"id":403282,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1010634,"name":"Philip J. Agostinelli","orcid":"0000-0002-0613-1031","position":1,"is_corresponding":false},{"id":1117293,"name":"Nicholas C. Bordonie","orcid":"0009-0007-5669-2172","position":2,"is_corresponding":false},{"id":1084728,"name":"Nina L. Stute","orcid":"0000-0001-8213-638X","position":3,"is_corresponding":false},{"id":798393,"name":"Braxton A. Linder","orcid":"0000-0001-6825-5622","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T01:20:36.280647Z","pmid":"36815729","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}