Adipose tissue macrophage populations and inflammation are associated with systemic inflammation and insulin resistance in obesity

Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 non-diabetic adults across a range of body mass indexes (BMI 20.5-45.8 kg/m2). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (SI) and beta cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, SI, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced SI, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-α (TNFα) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFα and CRP were negatively associated with SI, and circulating concentrations of TNFα and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity, and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.

Muscle Oxidative Capacity in the Arms and Legs of Various Types of Endurance Trained Athletes

Our study used near-infrared spectroscopy (NIRS) to measure muscle oxidative capacity (mVmax) in the medial gastrocnemius, vastus lateralis, biceps brachii, and wrist flexor muscles in Cross-country (LEG-T) and Swimmer/Rowers (WHOLE-T) and controls. Young male adults: cross-country LEG-Tners (n=6) and swimmers/rowers (n=5), moderately fit (CONTROL, n=7) were tested. mVmax was measured as the rate of post-exercise recovery of oxygen consumption after a short bout of exercise using NIRS. Whole-body peak oxygen uptake (VO2peak) was determined during a continuous treadmill protocol. The lower limb muscles had 42% higher mVmax than upper limb muscles in all subjects, with significant differences in 10 of 12 pairwise comparisons (p< 0.05). The LEG-T group had higher mVmax values in both legs than CONTROL group (p< 0.05), while the WHOLE-T group had higher mVmax in the vastus lateralis (p = 0.048). There were no differences in the arm muscles of between the groups. The combined mVmax of both leg muscles in all groups correlated with VO2peak (r2=0.597). Muscle oxidative capacity was consistent with training status, and leg mitochondrial capacity correlated with maximal whole body oxidative capacity. These results support the use of NIRS measurements to characterize oxidative capacity in skeletal muscles of athletic populations.

Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women

Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded.Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO2 max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity.Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo.Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.

NIRS-derived skeletal muscle oxidative capacity is correlated with aerobic fitness and independent of sex

Near-infrared spectroscopy (NIRS) can be used to measure skeletal muscle oxidative capacity. Here, we demonstrated that NIRS-derived skeletal muscle oxidative capacity of the vastus lateralis was independent of sex, reliable across and within days, and correlated with maximal and submaximal indices of aerobic fitness, including maximal oxygen uptake, lactate threshold, and respiratory compensation point. These findings highlight the utility of NIRS for investigating skeletal muscle oxidative capacity in females and males.

Comparative transcriptomic and metabolomic analysis reveals pectoralis highland adaptation across altitudinal songbirds

Background Pectoralis phenotypic variation plays a fundamental role in locomotion and thermogenesis in highland birds. However, its regulatory and metabolic mechanisms remain enigmatic to date. Here, we integrated phenomic, transcriptomic and metabolomic approaches to determine muscle variation and its underpinning mechanisms across altitudinal songbirds. Results Phenomics revealed that all highland birds had considerable increases in muscle oxidative capacity, capillarity, and mitochondrial abundance. Correspondingly, transcriptomic analyses found that differentially expressed genes in modules associated with phenotypes enriched in blood vessel, muscle structure development, and mitochondrial organization. Despite similar traits and functional enrichments across highland birds, different mechanisms drove their occurrence in part for their own various evolutionary histories. Importantly, a metabolic feature shared by highland birds is the improvement in insulin sensitivity and glucose utilization through activating insulin signaling pathway, which is vital to increase muscle oxidative capacity and maintain metabolic homeostasis. Nevertheless, fatty acid biosynthesis and oxidation are enhanced in species with a long evolutionary history, also differing from ketone body metabolism in recently introduced colonizer. Conclusions Our study represents a vital contribution to reveal the regulatory and metabolic basis of pectoralis variation across altitudinal songbirds.