title: Dissociating fatty liver and diabetes.
abstract: Fatty liver disease is epidemiologically associated with type 2 diabetes (T2D), leading to a speculation of a reciprocal cause-effect relationship and a vicious cycle of pathology. Here, we summarize recent literature reporting dissociation of hepatosteatosis from insulin resistance in genetic mouse models and clinical studies. We highlight rhythmic flows of metabolic intermediates between hepatic lipid synthesis and glucose production in normal circadian physiology. Blocking triglyceride (TG) secretion, subcellular lipid sequestration, lipolysis deficiency, enhanced lipogenesis, gluconeogenesis defects, or inhibition of fatty acid oxidation all result in hepatosteatosis without causing hyperglycemia or insulin resistance, suggesting that the cause-effect relationship between hepatosteatosis and diabetes does not exist in all situations.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice