title: The hepatic vagus mediates fat-induced inhibition of diabetic hyperphagia.
abstract: Diabetic rats both overeat high-carbohydrate diet and have altered hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). In contrast, a high-fat diet reduces caloric intake of diabetics to normal, reflected by normal hypothalamic NPY and CRF content. How the brain senses these changes in diet is unknown. To date, no hormonal changes explain these diet-induced changes in caloric intake. We tested whether the common branch of the hepatic vagus mediates the fat signal. We presented fat in two ways. First, diabetic and vehicle-treated rats were offered a cup of lard in addition to their normal high-carbohydrate diet. Second, we switched diabetic rats from high-carbohydrate diet to high-fat diet, without choice. In streptozotocin-treated rats, both methods resulted in fat-induced inhibition of caloric intake and normalization of hypothalamic neuropeptides to nondiabetic levels. Strikingly, common branch hepatic vagotomy (unlike gastroduodenal vagotomy) entirely blocked these fat-induced changes. Although a shift in hepatic energy status did not explain the lard-induced changes in diabetic rats, the data suggested that common hepatic branch vagotomy does not interfere with hepatic energy status. Furthermore, common branch hepatic vagotomy without diabetes induced indexes of obesity. Abnormal function of the hepatic vagus, as occurs in diabetic neuropathy, may contribute to diabetic obesity.
authors.affiliation: Department of Physiology, School of Medicine, University of California, San Francisco, San Francisco, California 94143-0444, USA. susanne@itsa.ucsf.edu
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Sotara L
authors.initials: SL
authors.lastname: Manalo
authors.forename: Mark I
authors.initials: MI
authors.lastname: Friedman
authors.forename: Mary F
authors.initials: MF
authors.lastname: Dallman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004041:Dietary Fats / Q000494:pharmacology*; D004386:Duodenum / Q000294:innervation; D004734:Energy Metabolism / Q000502:physiology; D006963:Hyperphagia / Q000378:metabolism / Q000503:physiopathology*; D008099:Liver / Q000294:innervation* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000294:innervation; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology* / Q000601:surgery
chemical_list: D004041:Dietary Fats; D000255:Adenosine Triphosphate; C029310:lard