Emilie A. Petersen

The interindividual variability in peak fat oxidation (PFO) and the intensity at which this occurs (Fat _max ) has been attributed to physiological factors, diet and physical activity; however, few studies have examined the contribution of skeletal muscle characteristics. The present study examined the relationship between PFO, Fat _max and the skeletal muscle proteome in young, physically active males. Thirty‐four young, lean males were phenotyped through assessment of aerobic capacity, PFO, body composition, fasting blood samples and a muscle biopsy. Liquid chromatography mass spectrometry based proteomics was used to assess skeletal muscle protein abundance. Only absolute PFO (g min ⁻¹ ) was positively correlated with ( r = 0.496, P =  0.003). Few skeletal muscle proteins correlated with absolute PFO, whereas relative PFO and Fat _max were positively associated with numerous mitochondrial proteins enriched in metabolic pathways, oxidative phosphorylation and other mitochondrial processes. Mitochondrial proteome abundance was positively correlated with both relative PFO ( r = 0.633, P <  0.001) and Fat _max ( r = 0.595, P <  0.001). Mitochondrial complex‐specific analysis demonstrated that respiratory complex V was associated with both relative PFO and Fat _max . Multiple regression analyses indicated that mitochondrial abundance and muscle glycogen explained 55% of the variability in relative PFO, whereas mitochondrial abundance alone explained 43% of the variability in Fat _max . Absolute PFO was explained by a combination of , mitochondrial abundance and muscle glycogen content ( r ² = 0.562). This untargeted proteomic approach highlights that skeletal muscle mitochondrial content contributes to the interindividual variability in PFO and Fat _max in lean, active young males. image Key points: This study used an untargeted proteomics approach to explore the links between the skeletal muscle proteome and peak fat oxidation (PFO) in young, physically active males. Absolute PFO was primarily associated with maximal aerobic capacity. When expressed relative to fat‐free mass, PFO was closely associated with skeletal muscle proteins enriched in oxidative metabolism and mitochondrial pathways. Mitochondrial abundance assessed by mitochondrial proteome content and citrate synthase activity was positively related to relative PFO and the intensity at which this occurs (Fat _max ). Mitochondrial respiratory complex V was consistently related to both relative PFO and Fat _max . Mitochondrial content independently contributed to both PFO and Fat _max , highlighting mitochondrial content as a key determinant of the maximal capacity for fat oxidation.

Background and objectives Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue. Methods Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336. Results A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and β-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT. Conclusions These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss.

Aim: To investigate effects of hormone replacement therapy in postmenopausal women on factors associated with metabolic flexibility related to whole‐body parameters including fat oxidation, resting energy expenditure, body composition and plasma concentrations of fatty acids, glucose, insulin, cortisol, and lipids, and for the mitochondrial level, including mitochondrial content, respiratory capacity, efficiency, and hydrogen peroxide emission.Methods: 22 postmenopausal women were included. 11 were undergoing estradiol and progestin treatment (HT), and 11 were matched non‐treated controls (CONT). Peak oxygen consumption, maximal fat oxidation, glycated hemoglobin, body composition, and resting energy expenditure were measured. Blood samples were collected at rest and during 45 min of ergometer exercise (65% VO₂peak). Muscle biopsies were obtained at rest and immediately post‐exercise. Mitochondrial respiratory capacity, efficiency, and hydrogen peroxide emission in permeabilized fibers and isolated mitochondria were measured, and citrate synthase (CS) and 3‐hydroxyacyl‐CoA dehydrogenase (HAD) activity were assessed.Results: HT showed higher absolute mitochondrial respiratory capacity and post‐exercise hydrogen peroxide emission in permeabilized fibers and higher CS and HAD activities. All respiration normalized to CS activity showed no significant group differences in permeabilized fibers or isolated mitochondria. There were no differences in resting energy expenditure, maximal, and resting fat oxidation or plasma markers. HT had significantly lower visceral and total fat mass compared to CONT.Conclusion: Use of hormone therapy is associated with higher mitochondrial content and respiratory capacity and a lower visceral and total fat mass. Resting energy expenditure and fat oxidation did not differ between HT and CONT.