title: β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia.
abstract: β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMB-enriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2α, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2α markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2α levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Zaira
authors.initials: Z
authors.lastname: Aversa
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonetto
authors.forename: Paola
authors.initials: P
authors.lastname: Costelli
authors.forename: Valerio Giacomo
authors.initials: VG
authors.lastname: Minero
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.forename: Francesco Maria
authors.initials: FM
authors.lastname: Baccino
authors.forename: Simone
authors.initials: S
authors.lastname: Lucia
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi Fanelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muscaritoli
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology / Q000517:prevention & control*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014631:Valerates / Q000494:pharmacology* / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D014631:Valerates; C004961:beta-hydroxyisovaleric acid