Chronic Exendin-4 Treatment Prevents the Development of Cancer Cachexia Symptoms in Male Rats Bearing the Yoshida Sarcoma

Abstract

Cancer cachexia is the syndrome of weight loss, loss of appetite, and wasting of skeletal muscle and adipose tissue experienced by many individuals with cancer. Currently, few effective treatment and prevention strategies are available for these patients, due in part to a poor understanding of the mechanisms contributing to cachexia. Insulin resistance has been associated with cancer cachexia in epidemiological, human, and animal research. The present experiment was designed to examine the ability of Exendin-4, a GLP-1 agonist and insulin sensitizing agent, to prevent the development of cachexia symptoms in male Sprague Dawley rats bearing the Yoshida sarcoma. Following tumor implantation or sham surgery, rats received daily treatment with saline or Exendin-4 (3 μg/kg body weight/day) and were monitored for tumor growth and cachexia symptoms for 21-23 days. As a result of large variability in treatment effects, data were analyzed separately for animals with large and small tumors. Exendin-4 treatment reduced tumor growth and prevented the development of cancer cachexia symptoms in animals with small, but not large, tumors. In addition, insulin levels were preserved in Exendin-4-treated tumor-bearing animals. The results of this experiment demonstrate a novel preventative therapy for cancer cachexia, and a novel use of Exendin-4. Further research is necessary to determine the mechanisms through which Exendin-4 exerts these potent effects.

Energy metabolism in cachexia

“…Altered glucose homeostasis and insulin sensitivity/insulin secretion have also been shown in cachexia , so a role for GLP‐1 is likely. Indeed, the GLP‐1 agonist and insulin sensitizer exendin‐4 partially prevents cachexia in tumor‐bearing rats . Recent evidence further suggests that brainstem GLP‐1 signaling influences body weight loss and lean/fat mass in cachectic rodents .…”

Diabetes pharmacotherapy and effects on the musculoskeletal system

“…Colin et al showed that myocytes from obese, nondiabetic Zucker rates were significantly enlarged and depleted of lipid droplets with exendin‐4 treatment, secondary to modulation of oxidative stress; Takada et al showed improved mitochondrial function and exercise capacity in mice receiving exendin‐4 . Exenatide was reported to prevent sarcoma‐induced cachexia in a mouse model, while liraglutide was shown to improve skeletal muscle capillary density in an animal model of insulin resistance, indicating a protective role against metabolic insulin resistance at the skeletal muscle level . Exenatide has also been shown to increase irisin, a myokine that is commonly induced by exercise, in patients with T2D .…”

Methodological validation of a vertical ladder with low intensity shock stimulus for resistance training in C57BL/6 mice: Effects on muscle mass and strength, body composition, and lactate plasma levels

“…The scanning of the member volume occurred in the network interface (Ethernet) where it enabled documentation in DICOM standard. Prior to this procedure, the animals were anesthetized with ketamine/ xylazine (75 mg/kg and 5 mg/kg body weight, respectively) (Close et al, 1996;Foster, Pavlin, Harasiewicz, Christopher, & Turnbull, 2000;Honors & Kinzig, 2014).…”

“…After 24 hours of the last assessment of limb volume, all animals were anesthetized again with ketamine/xylazine (75 mg/kg and 5 mg/kg body weight, respectively) and euthanized by cervical dislocation (Close et al, 1996;Foster et al, 2000;Honors & Kinzig, 2014) to perform the collection of skeletal muscle tissues of the quadriceps, visceral white adipose, and adipose brown scapular. The collected tissues were weighed using an analytical precision digital scale (A. Cientifica EEQ9003E) (Hansen, Han, Nolte, Chen, & Holloszy, 1997;Honors & Kinzig, 2014).…”