title: Fatty Liver and Fatty Heart-Where do They Stand in the AMIS Syndrome?
abstract: Meal-induced insulin sensitization (MIS) refers to the augmented glucose uptake response to insulin following a meal. Absence of MIS (AMIS) causes significant decrease in post-meal glucose disposal leading to postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, adiposity, increased free radical stress, and a cluster of progressive metabolic, vascular, and cardiac dysfunctions referred to as the AMIS syndrome. We tested the hypothesis that fat accumulation in the liver and heart is part of the AMIS syndrome. Questions examined in the study: (1) Is prediabetic fat accumulation in the heart and liver a component of the AMIS syndrome? (2) Is fatty liver a cause or consequence of peripheral insulin resistance? (3) Is early cardiac dysfunction in the AMIS syndrome attributable to fat accumulation in the heart? and (4) Can the synergistic antioxidant cocktail SAMEC (S-adenosylmethionine, vitamin E, and vitamin C), known to benefit MIS, affect cardiac and hepatic triglyceride levels? Four animal models of AMIS were used in aged male Sprague-Dawley rats (52 weeks ± sucrose ± SAMEC), compared with young controls (nine weeks). Fat accumulation in the heart was not significant and therefore cannot account for the early cardiac dysfunction. Hepatic triglycerides increased only in the most severe AMIS model but the small changes correlated with the much more rapidly developing peripheral adiposity. Systemic adiposity represents an early stage, whereas accumulation of cardiac and hepatic triglycerides represents a late stage of the prediabetic AMIS syndrome. Fat accumulation in the liver is a consequence, not a cause, of AMIS. SAMEC protected against the sucrose effects on whole body adiposity and hepatic lipid accumulation.
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. wlautt@cc.umanitoba.ca.
authors.forename: W Wayne
authors.initials: WW
authors.lastname: Lautt
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. zhi-ming@live.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ming
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. Dallas.Legare@umanitoba.ca.
authors.forename: Dallas J
authors.initials: DJ
authors.lastname: Legare
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. kawshik88@yahoo.com.
authors.forename: Kawshik K
authors.initials: KK
authors.lastname: Chowdhury
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. ghatch@chrim.ca.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. H.Helen.Wang@umanitoba.ca.
authors.forename: Hui Helen
authors.initials: HH
authors.lastname: Wang
keywords: S-adenosylmethionine; absence of meal-induced insulin sensitization (AMIS); hepatic insulin sensitizing substance (HISS); meal-induced insulin sensitization (MIS); non-alcoholic fatty liver disease (NAFLD); rapid insulin sensitivity test (RIST); vitamins E and C (SAMEC)