peptide-yy and Cachexia

Topics: Appetite; Cachexia; Energy Intake; Ghrelin; Humans; Hypothalamus; Obesity; Peptide Hormones; Peptide YY; Vagus Nerve

Peptide YY (PYY) is a naturally occurring gut hormone with mostly inhibitory actions on multiple tissue targets. PYY has been identified in several carcinoid tumors and a decreased expression of PYY may be relevant to the development and progression of colon adenocarcinoma. Treatment with PYY decreases growth in pancreatic and breast tumors, most likely through a reduction in intracellular cAMP. In cancer patients, PYY may also improve malnutrition that results from iatrogenic causes or cachexia associated with advanced disease. PYY plays a significant role in multiple aspects of cancer from regulation of cell growth to potential therapeutic applications.

Topics: Adenocarcinoma; Breast Neoplasms; Cachexia; Carcinoid Tumor; Cell Division; Colonic Neoplasms; Cyclic AMP; Humans; Pancreatic Neoplasms; Peptide YY; Time Factors

Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

Topics: Animals; Anorexia; Body Weight; Cachexia; Cell Line, Tumor; Chemokine CCL2; Drugs, Chinese Herbal; Ghrelin; Glucagon-Like Peptide 1; Inflammation; Interleukin-6; Intestinal Mucosa; Leptin; Male; Mice; Mice, Inbred BALB C; Muscles; Neoplasm Transplantation; Neoplasms; Peptide YY; Plant Preparations; Tumor Necrosis Factor-alpha

Topics: Adult; Appetite; Cachexia; Female; Ghrelin; Heart Failure; Humans; Hypertension, Pulmonary; Male; Peptide Hormones; Peptide YY; Postprandial Period; Satiation

Anorexia and weight loss are negative prognostic factors in patients with cancer. Although total ghrelin levels are increased in energy-negative states, levels of the biologically active octanoylated ghrelin and the anorexigenic peptide YY (PYY) have not been reported in patients with cancer-induced cachexia. We hypothesized that abnormal ghrelin and/or PYY levels contribute to cancer-induced cachexia. We evaluated 21 patients with cancer-induced cachexia; 24 cancer patients without cachexia; and 23 age-, sex-, race-, and BMI-matched subjects without cancer. Active ghrelin levels and the active to total ghrelin ratio were significantly increased in subjects with cancer-induced cachexia, compared with cancer and noncancer controls. PYY levels were similar among groups. Appetite measured by a visual analog scale was not increased in subjects with cachexia. The increase in active ghrelin levels is likely to be a compensatory response to weight loss. Cachexia may be a state of ghrelin resistance because appetite does not correlate with ghrelin levels. Changes in the active to total ghrelin ratio suggest that a mechanism other than increased secretion must be responsible for the increase in active ghrelin levels. PYY is unlikely to play an important role in cancer-induced cachexia.

Topics: Aged; Appetite; Cachexia; Ghrelin; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Interleukin-6; Middle Aged; Neoplasms; Peptide Hormones; Peptide YY; Serum Albumin; Tumor Necrosis Factor-alpha

Prevention of gut hypoplasia associated with total parenteral nutrition (TPN) was investigated in 67 adult male Fisher 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 beta-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.

Topics: Adrenergic beta-Agonists; Animals; Cachexia; Clenbuterol; Combined Modality Therapy; Drug Synergism; Intestinal Mucosa; Intestine, Small; Male; Parenteral Nutrition, Total; Peptide YY; Proteins; Rats; Rats, Inbred F344; Sarcoma, Experimental