Browsing by Author "Alotaibi, Mohammed I"

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Metabolic and Molecular Changes in Visceral Obesity
(Saudi Digital Library, 2025) Alotaibi, Mohammed I; Murphy, David; Greenwood, Michael
Rodent models have played a crucial role in obesity research, particularly for understanding polygenic obesity, which mirrors human obesity more closely than monogenic forms. The genetically diverse outbred Crl:CD SD rats provide a relevant system for studying obesity-related metabolic changes. This study categorized male Crl:CD SD rats into overweight, average-weight, and underweight groups based on body weight percentiles. Without intervention, the overweight rats exhibited increased food intake, adiposity, hyperinsulinemia, hyperglycemia, and hyperleptinemia, reinforcing their suitability for studying polygenic obesity. Expanding on these findings, a multi-omics approach was employed to investigate molecular differences in epididymal white adipose tissue (EWAT). Proteomics, phospho-proteomics, and kinase activity assays revealed significant alterations in adipogenesis pathways, cell cycle regulation, inflammatory markers, and insulin signaling. Notably, overweight rats demonstrated increased activity of the dual specificity mitogen activated protein kinase 7 (MKK7) and the never in mitosis gene A (NEK2), alongside hyperphosphorylation of O-GlcNAcase (OGA) at serine 364. To further assess the functional roles of these proteins, gene knockdown experiments were conducted in 3T3-L1 adipocytes. While Mkk7 knockdown did not impair adipogenesis, it influenced cytokine production, suggesting a role in adipose tissue inflammation. Conversely, Oga knockdown resulted in reduced cell viability and impaired adipogenesis, highlighting its importance in adipocyte differentiation. Taken together, these findings establish Crl:CD SD rats as a valuable model for studying polygenic visceral obesity and its molecular underpinnings. Additionally, MKK7 and OGA emerge as potential therapeutic targets for mitigating adipose tissue inflammation and visceral adiposity, though further in vivo studies are required to elucidate their specific mechanisms.
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