1. The effect of succinic acid on the metabolic profile in high‐fat diet‐induced obesity and insulin resistance
- Author
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Thomas H. Reynolds, Caty Sheridan, Sarita Lagalwar, Kavey Vidal, Saada Legesse, Stephen J. Ives, Cheyanne Slocum, Kendall S. Zaleski, and Daniela Escudero
- Subjects
Male ,obesity ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Succinic Acid ,Type 2 diabetes ,White adipose tissue ,030204 cardiovascular system & hematology ,Diet, High-Fat ,lcsh:Physiology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,mitochondrial function ,Physiology (medical) ,Internal medicine ,Respiration ,medicine ,Animals ,Original Research ,lcsh:QP1-981 ,Chemistry ,Insulin ,Body Weight ,digestive, oral, and skin physiology ,food and beverages ,Metabolism ,medicine.disease ,Mice, Inbred C57BL ,Endocrinology ,Mitochondrial biogenesis ,Metabolome ,Blood sugar regulation ,type 2 diabetes ,Insulin Resistance ,Energy Metabolism ,metabolism ,030217 neurology & neurosurgery - Abstract
Obesity, insulin resistance, and poor metabolic profile are hallmarks of a high‐fat diet (HFD), highlighting the need to understand underlying mechanisms. Therefore, we sought to determine the effect of succinic acid (SA) on metabolism in high‐fat diet (HFD)‐induced obesity. Animals were randomly assigned to either low‐fat diet (LFD) or a high‐fat diet (HFD). Mice consumed their respective diets for 4.5 months and then assigned to the following groups: (LFD)+vehicle, LFD + SA (0.75 mg/ml), HFD + vehicle, or HFD + SA. Body weight (BW), food, and water intake, were tracked weekly. After 6 weeks, insulin, glucose, and pyruvate tolerance tests were completed, and spontaneous physical activity was assessed. Epididymal white adipose tissue (EWAT) mass and in vitro measurements of oxidative skeletal muscle (soleus) respiration were obtained. Expectedly, the HFD increased BW and EWAT mass, and reduced glucose and insulin tolerance. SA significantly reduced EWAT mass, more so in HFD (p .05). A significant (p, Obesity, insulin resistance, and poor metabolic profile are hallmarks of a high‐fat diet (HFD), highlighting the need to understand underlying mechanisms and potential treatments. In the HFD‐induced model of obesity, with marked insulin resistance, we treated mice with succinic acid, a metabolite, and complex II agonist. Succinic acid had no positive effect on glucose regulation, but seemed to reduce adiposity, and increase mitochondrial respiratory capacity in oxidative skeletal muscle, likely due to a succinic acid‐induced mitochondrial biogenesis.
- Published
- 2020