Ceddia, RolandoJani, Shailee Bhavan2023-08-042023-08-042023-08-04https://hdl.handle.net/10315/41360This dissertation explores the role of intermediary lipid accumulation in the development of tissue specific and whole-body insulin resistance (IR). In this context, we investigated whether the intramyocellular lipid accumulation was sexually dimorphic, whether it differed between oxidative and glycolytic muscles, and how it correlated with high-fat sucrose-enriched (HFS) diet-induced skeletal muscle IR. To accomplish that, male and female Wistar rats were either fed a standard chow (SC) or a HFS diet for 8 weeks. Broadly, highly oxidative male muscles had impaired insulin sensitivity associated with the activation of PKCδ and θ isoforms in soleus (Sol, rich in type IA fibers), extensor digitorum longus (EDL, rich in type 2A fibers). In the highly glycolytic epitrochlearis (Epit, rich in type IIB fibers) muscles, impaired insulin sensitivity was associated with the upregulation of inflammatory mediators. In females, the HFS diet also led to a significant elevation in intramuscular DAG and TAG contents; however, without any alteration in ceramides levels in insulin-resistant female oxidative and glycolytic muscles. Moreover, a pro-inflammatory response was observed in skeletal muscles rich in type IIa and type IIb of female rats fed a HFS diet. Hence, based on my findings, all muscles from male and female rats fed the obesogenic diet developed IR, although the underlying associated mechanisms differed with respect to muscle fiber-type distribution in males and females.Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.KinesiologyNutritionMolecular biologyElectronic Thesis or Dissertation2023-08-04DiabetesObesitySkeletal muscleLiverGlucose metabolismInsulin resistance