title: From a glucocentric to a lipocentric approach towards metabolic syndrome.
abstract: Insulin resistance, the essential component of metabolic syndrome, has traditionally been defined from a glucocentric viewpoint, with glucotoxicity playing a lead role. However, as overabundant circulating fatty acids are now known to be overt contributors, there is a paradigm shift in the understanding of metabolic syndrome acknowledging the importance of lipotoxicity as a major perpetuator of insulin resistance. Ectopic accumulation of fat in liver, adipose, muscle and pancreatic islets, provokes insulin resistance through various mechanisms. Chronic inflammation/adipocytokine generation, endoplasmic reticulum stress and mitochondrial dysfunction/oxidative stress also contribute significantly towards insulin resistance. Targets that can act as counter regulators/master switches at the converging point of all these metabolic pathways are currently under intense development.
authors.affiliation: Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, R&D III, Plot No. 20, Sector 18, Udyog Vihar Industrial Area, Gurgaon 122 001, Haryana, India. shivani.mittra@ranbaxy.com
authors.forename: Shivani
authors.initials: S
authors.lastname: Mittra
authors.forename: Vinay S
authors.initials: VS
authors.lastname: Bansal
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Bhatnagar
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000375:Aging / Q000502:physiology; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D005234:Fatty Liver / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000502:physiology; D008060:Lipodystrophy / Q000151:congenital / Q000378:metabolism; D050155:Lipogenesis; D024821:Metabolic Syndrome / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress
chemical_list: D005230:Fatty Acids, Nonesterified