Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H2O2 emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H2O2 emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance.

Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m²; n = 10) and obese (BMI: 34.7 ± 3.5 kg/m²; n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects ( P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects ( P = 0.02) and was correlated with SCAT lipolysis ( r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese ( P < 0.01), but exercise-induced SCAT lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean ( P = 0.04) but suppressed lipolysis in obese ( P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown.

The purpose of the study was to examine how modifiable maternal factors (body mass index (BMI), household income, fatigue, sleep, breastfeeding status, diet, and physical activity) relate to postpartum depression (PPD) at 6 and 12 months postpartum. Participants (n = 26) participated in two study visits (6 and 12 months postpartum) where vitals, weight, body composition (skinfold anthropometrics), and physical activity levels (Actigraph GTX9 accelerometer) were assessed. Validated instruments (BRUMS-32, Subjective Exercise Experience Scale, Pittsburg Sleep Quality index, NIH breastfeeding survey, NIH Dietary History Questionnaire, and Edinburg Postnatal Depression Scale) assessed lifestyle and demographic factors of interest. PPD at six months was correlated to PPD at 12 months (r = 0.926, p < 0.001). At six months postpartum, PPD was positively correlated to BMI (r = 0.473, p = 0.020) and fatigue (r = 0.701, p < 0.001), and negatively correlated to household income (r = −0.442, p = 0.035). Mothers who were breastfeeding had lower PPD scores (breastfeeding 3.9 ± 3.5 vs. not breastfeeding 7.6 ± 4.8, p = 0.048). At 12 months, PPD was positively correlated to sleep scores (where a higher score indicates poorer sleep quality) (r = 0.752, p < 0.001) and fatigue (r = 0.680, p = 0.004). When analyzed collectively via regression analyses, household income and fatigue appeared to be the strongest predictors of PPD at six months postpartum.

The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity.