Deena B Snoke1, Yuko Nishikawa2, Rachel M Cole1, Ai Ni3, Austin Angelotti1, Yael Vodovotz2, Martha A Belury4. 1. Interdisciplinary PhD Program in Nutrition, The Graduate School, The Ohio State University, Columbus, OH, USA. 2. Department of Food Science and Technology, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Columbus, OH, USA. 3. Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH, USA. 4. Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA.
Abstract
SCOPE: Cancer cachexia is characterized by the loss of skeletal muscle resulting in functional impairment, reduced quality of life and mortality. Naringenin, a flavonoid found in citrus fruits, improves insulin sensitivity and reduces inflammation and tumor growth in preclinical models. Therefore, the study hypothesizes that dietary supplementation of naringenin will improve insulin sensitivity, decrease inflammation, slow body weight loss, and delay tumor growth in a mouse model of cancer cachexia. METHODS AND RESULTS: Mice are fed 2 wt% dietary naringenin before and during initiation of cancer cachexia using inoculated adenocarcinoma-26 cells (C-26). Food intake, body weight, body composition, muscle function, insulin tolerance, and inflammatory status are assessed. Although naringenin-fed tumor-bearing mice exhibit reductions in body weight and food intake earlier than control diet-fed tumor-bearing mice, dietary naringenin is protective against loss of muscle strength, and attenuates the onset of insulin resistance and markers of inflammation. CONCLUSIONS: Dietary supplementation of naringenin improves multiple aspects of metabolic disturbance and inflammation during cancer cachexia progression in [C-26 tumor-bearing] mice. However, the acceleration of anorexia and weight loss is also observed. These findings emphasize the link between inflammation and insulin resistance as a basis for understanding their roles in the pathogenesis of cancer cachexia.
SCOPE: Cancer cachexia is characterized by the loss of skeletal muscle resulting in functional impairment, reduced quality of life and mortality. Naringenin, a flavonoid found in citrus fruits, improves insulin sensitivity and reduces inflammation and tumor growth in preclinical models. Therefore, the study hypothesizes that dietary supplementation of naringenin will improve insulin sensitivity, decrease inflammation, slow body weight loss, and delay tumor growth in a mouse model of cancer cachexia. METHODS AND RESULTS: Mice are fed 2 wt% dietary naringenin before and during initiation of cancer cachexia using inoculated adenocarcinoma-26 cells (C-26). Food intake, body weight, body composition, muscle function, insulin tolerance, and inflammatory status are assessed. Although naringenin-fed tumor-bearing mice exhibit reductions in body weight and food intake earlier than control diet-fed tumor-bearing mice, dietary naringenin is protective against loss of muscle strength, and attenuates the onset of insulin resistance and markers of inflammation. CONCLUSIONS: Dietary supplementation of naringenin improves multiple aspects of metabolic disturbance and inflammation during cancer cachexia progression in [C-26 tumor-bearing] mice. However, the acceleration of anorexia and weight loss is also observed. These findings emphasize the link between inflammation and insulin resistance as a basis for understanding their roles in the pathogenesis of cancer cachexia.
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