Hypercytolipidemia-induced cellular lipoapoptosis: cytostructural and endometabolic basis of progressive organo-involution following expression of diabetes (db/db) and obese (ob/ob) mutation syndromes.
Onset expression of Type 2 (NIDDM) diabetes and obesity metabolic syndromes (DOS) are characterized by premature, progressive cytoatrophy and organo-involution induced by dysregulated cellular gluco- and lipo-metabolic cascades. The consequential systemic, interstitial and intracellular hyperlipidemia disrupts normal cytointegrity and metabolic responsivity to the established hypercaloric pericellular environments. The sequential cytostructural, metabolic and endocrine disturbances associated with the development of progressive DOS-associated hypercytolipidemia compromises cellular metabolic response cascades and promotes cytochemical disturbances which culminate with nuclear lipoapoptosis and cytoatrophy. The dramatic alterations in interstitial glucose and lipid (free fatty acids/triglycerides) concentrations are recognized to influence interstitial and cytoplasmic microchemical environments, which markedly alter cellular nutrient diffusion and active trans-membrane flux rates. The progressive exacerbation of interstitial and cytoplasmic lipid imbibition has been demonstrated to be associated with DNA fragmentation by lipo-infiltration into the chromatin matrix, inducing structural disruption and physical dissolution, indexed as nuclear lipoapoptosis. Therapeutic reduction of the severity of hypercytolipidemia-induced structural and cytochemical compromise promotes the restoration of homeostatic metabolic support for normalized cytostructural indices and supportive cellular gluco- and lipo-metabolic cascades. The re-establishment of a homeostatic interstitial microenvironment moderates the severity of cytolipidemic compromise within affected cell types, reduces nuclear lipo-infiltration and DNA lipo-dissolution, resulting in the preservation of cytostructural integrity. Through the therapeutic restoration of extra- and intra-cellular microchemical environments in genetically dysregulated metabolic syndrome models, the coincident cytochemical, endocrine and metabolic disturbances associated with progressive hypercytolipidemia, resulting from the expressed systemic hypercaloric environmental and hepato-pancreatic endometabolic disturbances which characterize Type 2 (NIDDM) diabetes-obesity and metabolic (X) syndromes, may be ameliorated.
Garris
David R
DR
Division of Cell Biology, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA. garrisd@umkc.edu
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000235:genetics; D009154:Mutation; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D013577:Syndrome
D051017:Apoptosis Regulatory Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin