Sex-specific effects of maternal and postweaning high-fat diet on skeletal muscle mitochondrial respiration.

Exposure to maternal over-nutrition in utero is linked with developmental programming of obesity, metabolic syndrome and cardiovascular disease in offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal muscle mitochondrial function contributes to substrate metabolism and is impaired in metabolic disease. We examined muscle mitochondrial respiration in male and female mice exposed to maternal HF diet in utero, followed by postweaning HF diet until middle age. After in utero exposure to maternal control (Con) or HF diet (45% kcal fat; 39.4% lard, 5.5% soybean oil), offspring were weaned to Con or HF, creating four groups: Con/Con (male/female (m/f), n=8/8), Con/HF (m/f, n=7/4), HF/Con (m/f, n=9/6) and HF/HF (m/f, n=4/4). Oxidative phosphorylation (OXPHOS) and electron transfer system (ETS) capacity were measured in permeabilized gastrocnemius bundles. Maternal HF diet increased fasting glucose and lean body mass in males and body fat percentage in both sexes (P⩽0.05). Maximal adenosine diphosphate-stimulated respiration (complex I OXPHOS) was decreased by maternal HF diet in female offspring (-21%, P=0.053), but not in male (-0%, P>0.05). Sexually divergent responses were exacerbated in offspring weaned to HF diet. In females, OXPHOS capacity was lower (-28%, P=0.041) when weaned to high-fat (HF/HF) v. control diet (HF/Con). In males, OXPHOS (+33%, P=0.009) and ETS (+42%, P=0.016) capacity increased. Our data suggest that maternal lard-based HF diet, rich in saturated fat, affects offspring skeletal muscle respiration in a sex-dependent manner, and these differences are exacerbated by HF diet in adulthood.

Candidate mechanisms underlying effects of contractile activity on muscle morphology and energetics in cancer cachexia.

Skeletal muscle wasting is a prominent pathophysiological feature of cancer cachexia. Recent evidence suggests the manifestation of mitochondrial dysfunction along with a diminished oxidative capacity. These abnormalities have been concurrently observed with impaired muscle force production and the accelerated onset of fatigue in both tumour-bearing animals and cancer patients exhibiting wasting. To address the burden imposed by cachexia, nutritional and pharmacological interventions have been investigated extensively; in contrast, contractile activity-based countermeasures (i.e. exercise training) have been less frequently explored. Although limited, several preclinical studies that implemented contractile activity have reported favourable outcomes such as the retention of muscle mass and the restoration of energetic homeostasis. Even fewer investigations have examined the mechanisms accounting for these protective effects. An experimental approach addressing contractile activity-dependent expression of muscle mass and energy metabolism regulators may yield information that provides mechanistic support for exercise countermeasures. In this review, we present several candidate mechanisms underlying the protective effects of contractile activity as support for exercise countermeasure strategies. Given the limited quantity of data in this area, insights will be derived from studies on contractile activity-dependent modulation of common cellular and molecular events regulating muscle morphology and energetics during other muscle wasting conditions (e.g. sarcopenia).