This study was conducted to determine the fatty acid (FA) content in pasture grasses, legumes, and non-leguminous forbs in northeast West Virginia. Grass, legume, and forb plant material were collected from rotationally stocked pastures and analyzed for crude protein (CP), linoleic acid (C18:2), α-linolenic acid (C18:3), and total FA content. Species within botanical classes varied in FA content. Forbs had the highest linoleic acid (C18:2) content followed by legume and grass species. Grasses and forbs had the highest α-linolenic acid (C18:3) content. Forbs had the highest total FA content. These field data were combined with FA data from the research literature to evaluate the correlation of CP concentration with fatty acid concentration. Likewise, after accounting for CP, the summer months caused a decrease while forbs caused an increase in α-linolenic acid (C18:3) content. Vegetative growth and leafiness are the major determinants of FA content in pasture forage. Grazing management to benefit vegetative growth and the presence of desirable forbs in tune with seasonal changes are valuable tools to increase desirable FA profiles in milk and meat products that may be of benefit to human health.

Background/Objectives: Breast cancer (BC) is the second most commonly diagnosed cancer worldwide and is accompanied by fatigue during both active disease and remission in the majority of cases. Our lab has measured fatigue in isolated muscles from treatment-naive BC patient-derived orthotopic xenograft (BC-PDOX) mice. Here, we conducted a preclinical trial of pioglitazone in BC-PDOX mice to determine its efficacy in ameliorating BC-induced muscle fatigue, as well as its effects on transcriptomic, metabolomic, and lipidomic profiles in skeletal muscle. Methods: The pioglitazone and vehicle groups were treated orally for 4 weeks upon reaching a tumor volume of 600 mm³. Whole-animal indirect calorimetry was used to evaluate systemic metabolic states. The transcriptome was profiled using short-read bulk RNA sequencing (RNA-seq). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to profile the metabolome and lipidome. Fast and slow skeletal muscle function were evaluated using isolated ex vivo testing. Results: Pioglitazone was associated with a 16.634% lower average O₂ consumption (mL∙h⁻¹, p = 0.035), 16.309% lower average CO₂ production (mL∙h⁻¹, p = 0.022), and 16.4% lower cumulative energy expenditure (EE) (kcal∙h⁻¹, p = 0.035), with no changes in substrate utilization. RNA-seq supported the downstream effects of pioglitazone on target genes and displayed considerable upregulation of mitochondrial bioenergetic pathways. K-means cluster 5 showed enrichment of the PPAR signaling pathway (adj. p < 0.05, Log2FC = 2.58). Skeletal muscle metabolomic and lipidomic profiles exhibited dysregulation in response to BC, which was partially restored in pioglitazone-treated mice compared to vehicle-treated BC-PDOX mice. In particular, the overall abundance of total ceramide levels was significantly lower in the PioTx group (−46.327%, p = 0.048). Despite molecular support for pioglitazone’s efficacy, isolated muscle function was not affected by pioglitazone treatment. No significant difference in the area under the fatigue curve (AUC) was found between the pioglitazone and vehicle groups (p = 0.596). Conclusions: BC induces multi-omic dysregulation in skeletal muscle, which pioglitazone partially ameliorates. Future research should focus on profiling systemic metabolic dysfunction, identifying molecular biomarkers of fatigue, and testing alternative pioglitazone treatment regimens.

Cool-season grass samples were collected and analyzed for omega-6 and omega-3 fatty acid (FA) content. Perennial ryegrass, tall fescue, orchardgrass, and Kentucky bluegrass samples were collected on four harvest dates from various trials conducted in the eastern portion of the Appalachian Mountains. There was a greater change in linolenic acid (C18:3) than linoleic acid (C18:2) concentrations in all forage species and across seasons. Perennial ryegrass had higher levels of linolenic acid compared to the other grasses on most dates other than in August, when it did not provide forage. Linoleic acid concentrations changed less across seasons and were generally lower in tall fescue compared to the other grass species, which tended to contain similar levels. There was a species × date interaction on FA concentrations. Kentucky bluegrass had a peak concentration of linoleic acid in August. Concentration in orchardgrass fluctuated slightly across seasons, while concentrations in tall fescue and perennial ryegrass decreased as the season advanced. Identification of FA concentrations in plant species and managing species diversity in pastures to increase and stabilize the content of omega-3 FA in meat and milk products appears to be a valuable tool for managers to manipulate FA characteristics of products from pasture-based systems.

Breast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis result in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that the isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest that these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within the muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations.