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Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1.

ABSTRACT: Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1). Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure. We further establish that thermogenic ROS alter the redox status of cysteine thiols in brown adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this site desensitizes the purine-nucleotide-inhibited state of the carrier to adrenergic activation and uncoupling. These studies identify mitochondrial ROS induction in brown adipose tissue as a mechanism that supports UCP1-dependent thermogenesis and whole-body energy expenditure, which opens the way to improved therapeutic strategies for combating metabolic disorders.

SUBMITTER: Chouchani ET

PROVIDER: S-EPMC5549630 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1.

Chouchani Edward T ET Kazak Lawrence L Jedrychowski Mark P MP Lu Gina Z GZ Erickson Brian K BK Szpyt John J Pierce Kerry A KA Laznik-Bogoslavski Dina D Vetrivelan Ramalingam R Clish Clary B CB Robinson Alan J AJ Gygi Steve P SP Spiegelman Bruce M BM

Nature 20160330 7597

Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1). Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supp ...[more]

PMID: 27027295

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Project description:BackgroundThermogenic supplements are often consumed by individuals seeking to improve energy levels and reduce body fat. These supplements are sold in powdered or ready-to-drink (RTD) forms and consist of a blend of ingredients such as caffeine, green tea extract, and other botanical compounds. While there is evidence that thermogenic supplements can positively affect resting energy expenditure (REE), the effect varies based on the combination of active ingredients. Additionally, there is some concern that thermogenic supplements may cause unwanted side effects on hemodynamic variables, like heart rate (HR) and blood pressure (BP). Therefore, further investigation into the efficacy and safety of commercially available products is warranted.MethodsTwenty-eight individuals (14 F, 14 M; age: 23.3 ± 3.9 yrs; height: 169.4 ± 8.6 cm; body mass: 73.3 ± 13.1 kg) completed two visits in a randomized, double-blind, crossover fashion. Each visit began with baseline REE, HR, and BP assessments, which were followed by ingestion of an active RTD thermogenic beverage (RTD; OxyShred Ultra Energy) or placebo (PL). Assessments were repeated at the intervals of 35-50- and 85-100-minutes post-ingestion. In addition, subjective outcomes of energy, focus, concentration, alertness, and mood were collected five times throughout each visit. Repeated-measures analysis of variance was performed with condition and time specified as within-subjects factors and sex and resistance training (RT) status as between-subjects factors. Statistical significance was accepted at p < 0.05.ResultsA significant condition × time interaction was observed for REE (p < 0.001). Higher REE values were demonstrated at 35-50 min (0.08 ± 0.02 kcal/min; p = 0.001; 5.2% difference) and 85-100 min (0.08 ± 0.02 kcal/min; p = 0.001; 5.5% difference) after RTD ingestion as compared to PL. No significant condition × time interactions were observed for respiratory quotient, HR, or BP. Condition main effects indicated lower HR (3.0 ± 0.9 bpm; p = 0.003), higher SBP (3.5 ± 1.1 mm Hg; p = 0.003) and higher DBP (3.5 ± 0.9 mm Hg; p < 0.001) in RTD as compared to PL, irrespective of time. Condition × time interactions were observed for all subjective outcomes (p ≤ 0.02). Post hoc tests indicated statistically significant benefits of the RTD over PL for energy, focus, concentration, and alertness, without significant differences for mood after correction for multiple comparisons. Sex and RT status were not involved in interactions for any outcomes, except for a Sex × RT status interaction for energy, indicating higher energy ratings in non-resistance-trained vs. resistance-trained males.ConclusionsThese data suggest that acute ingestion of a thermogenic RTD beverage significantly increases REE, and this elevated caloric expenditure is sustained for at least 100 minutes following ingestion. Furthermore, the RTD beverage increased measures of energy, focus, concentration, and alertness as compared to placebo. While minor differences in hemodynamic variables were observed between conditions, all values stayed within normal ranges. Individuals aiming to increase energy expenditure may benefit from acute ingestion of an RTD thermogenic supplement.

Dataset Information

Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1.

Publications

Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1.

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