Reduction of gut hypoplasia and cachexia in tumor-bearing rats maintained on total parenteral nutrition and treated with peptide YY and clenbuterol

Prevention of gut hypoplasia associated with total parenteral nutrition (TPN) was investigated in 67 adult male Fischer 344 rats. Mass and protein content of the small intestine was reduced by 31% and 39%, respectively, after 7 d of TPN in tumor-bearing (TB) rats. Coinfusing peptide YY (PYY; 1 nmol · kg−1 · h−1) and treating the rats with the anabolic β-adrenergic agonist, clenbuterol (CLE; 2 mg · kg−1 · d−1), resulted in significant savings in small intestine weight (26% increase) and protein (42% increase). Although the colon also exhibited a significant decrease in mass (31%), none of the treatment combinations were effective in this region of the gut. Histologic analysis of ileum suggested that the additive effects of PYY and CLE were due to differential effects of these compounds on mucosal and muscular tissues, respectively. This combination of treatments also resulted in significant savings (30% increase) in gastrocnemius protein, suggesting a reduction in the cachectic response. These results suggest that TPN-induced gut hypoplasia and cancer cachexia may be reduced by the proper combination of nutritional, hormonal, and pharmacologic treatments. In addition, the anabolic effects of various treatments may be additive to counteract TPN-induced gut atrophy.