Carbon Monoxide and Exercise Prevents Diet-Induced Obesity and Metabolic Dysregulation Without Affecting Bone.

Abstract

Objective

Carbon monoxide (CO) may counteract obesity and metabolic dysfunction in rodents consuming high-fat diets, but the skeletal effects are not understood. This study investigated whether low-dose inhaled CO (250 ppm) with or without moderate intensity aerobic exercise (3 h/wk) would limit diet-induced obesity and metabolic dysregulation and preserve bone health.

Methods

Obesity-resistant (OR) rats served as controls, and obesity-prone (OP) rats were randomized to sedentary, sedentary plus CO, exercise, or CO plus exercise. For 10 weeks, OP rats consumed a high-fat, high-sucrose diet, whereas OR rats consumed a low-fat control diet. Measurements included indicators of obesity and metabolism, bone turnover markers, femoral geometry and microarchitecture, bone mechanical properties, and tibial morphometry.

Results

A high-fat, high-sucrose diet led to obesity, hyperinsulinemia, and hyperleptinemia, without impacting bone. CO alone led only to a modest reduction in weight gain. Exercise attenuated weight gain and improved the metabolic profile; however, bone fragility increased. Combined CO and exercise led to body mass reduction and a metabolic state similar to control OR rats and prevented the exercise-induced increase in bone fragility.

Conclusions

CO and aerobic exercise training prevent obesity and metabolic sequelae of nutrient excess while stabilizing bone physiology.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1002/oby.22768

Publication Info

Gasier, Heath G, Tianzheng Yu, Joshua M Swift, Corrine E Metzger, Erin M McNerny, Elizabeth A Swallow, Claude A Piantadosi, Matthew R Allen, et al. (2020). Carbon Monoxide and Exercise Prevents Diet-Induced Obesity and Metabolic Dysregulation Without Affecting Bone. Obesity (Silver Spring, Md.), 28(5). pp. 924–931. 10.1002/oby.22768 Retrieved from https://hdl.handle.net/10161/24092.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Gasier

Heath Gasier

Associate Professor in Anesthesiology

Dr. Gasier is a physiologist and nutritionist. His research is focused on understanding how breathing altered PO2 impacts cell physiology in the lung, brain, and skeletal muscle. Emphasis is placed on mitochondrial quality control (dynamics, mitophagy, and biogenesis) and bioenergetics. He uses in vivo and in vitro models, and employs an array of methods (e.g., confocal and electron microscopy, Seahorse respiration, immunoblotting, RT-qPCR, ELISA’s, isotope tracers, and 10X genomics) for hypothesis testing. The goal of his research is to improve the operational capacity of divers and safety of hyperoxia in hyperbaric and critical care medicine. Dr. Gasier believes in a hands-on mentoring approach and individualized training plans based on mentee’s aspirations. He is committed to lifetime learning and contributing to knowledge advancement. 

Piantadosi

Claude Anthony Piantadosi

Professor Emeritus of Medicine

Dr. Piantadosi's laboratory has special expertise in the pathogenic mechanisms of acute organ failure, particularly acute lung injury (ALI), with an emphasis on the molecular regulatory roles of the physiological gases— oxygen, carbon monoxide, and nitric oxide— as they relate to the damage responses to acute inflammation. The basic science focuses on oxidative processes and redox-regulation, especially the molecular mechanisms by which reactive oxygen and nitrogen species transmit biological signals involved in the maintenance of energy metabolism and mitochondrial health, but also contribute to pathogenesis and to the resolution of tissue injury.

Clinically, ALI and the related syndrome of multiple organ failure has a high mortality, which is related to the host inflammatory response, but is not well understood scientifically; thus, the laboratory is devoted to understanding these mechanisms in the context of the host response to relevant but well-controlled experimental manipulations including hyperoxia, bacterial infections, toxic drugs, and cytokine/chemokine signals. The approach relies on animal models, mainly transgenic and knockout mice, and cell models, especially lung and heart cells to evaluate and understand the physiology, pathology, and cell and molecular biology of the injury responses, to test independent and integrated mechanisms, and to devise interventions to prevent damage.

Apart from the lung, significant work is devoted to understanding damage to the heart, brain, liver, and kidney caused by these immune mechanisms, specifically emphasizing the role of mitochondria, key targets and sources of oxidative damage. This damage compromises their ability to support energy homeostasis and advanced cellular functions, and impacts on the important roles these organelles play in cell death by apoptosis and necrosis as well as in the resolution of cellular damage and inflammation.


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