Date of Award
Hypometabolism is an important energy saving, highly regulated physiological response for some mammals; however, its mechanisms of control have yet to be fully described. It induces a reduction in metabolic rate, heart rate, blood pressure and body temperature. Although the degree and rate of body temperature decrease is subject to ambient temperatures, mammals still maintain control over the whole process. A major goal of hypometabolism appears to be maintaining energetic stores within the body as external food sources become sparse. Uncovering the mechanisms by which these mammals control this process is of interest as organ and tissue damage following hypometabolism, is rarely, if ever present. 5’adenosine monophosphate (5’AMP) has been demonstrated in this lab and others to induce a hypometabolic state in mice. Other molecules, such as TAN-67, a highly specific δ-opioid receptor agonist is able to induce hypometabolism and protect the brain from hypoxic conditions. A putative connection between these signaling molecules is possible at 5’AMP-activated protein kinase (AMPK). AMPK has an intimate role in metabolic processes throughout the body including roles in signaling and managing metabolic organelles. Understanding this mechanism could lead to potential therapeutic intervention in humans in areas following major surgery and organ transplantation. The aim of the present study is to test the hypothesis that murine hypometabolism induced by TAN-67 and 5’AMP respectively is characteristic of a signaling pathway homology. Male CD-1 mice were treated with one of the agonists: TAN-67 (4 mg/kg) or 5’AMP (400 mg/kg), followed by one of the antagonists, Naloxone (20 mg/kg) or Aminophylline (20 mg/kg), with saline serving as a control (n=3/group). During the trials measurements of flow of oxygen, flow of carbon dioxide and respiratory exchange ratio were followed for indirect calorimetry. Results indicate that 5’AMP, but not TAN-67 at the present dose was successful in inducing hypometabolism. Changes in dosage could be necessary to induce hypometabolism by TAN-67.
Hollinger, Trevor Thomas, "Murine Hypometabolism: A Putative Signaling Pathway." (2016). Dickinson College Honors Theses. Paper 240.