The effect of succinic acid on the metabolic profile in high‐fat diet‐induced obesity and insulin resistance

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), but had no effect on any in vivo measurements (BW, insulin, glucose, or pyruvate tolerance, nor physical activity, all p > .05). A significant ( p < .05) interaction was observed between mitochondrial respiration and treatment, where SA increased respiration, likely owed to greater mitochondrial content, as assessed by complex IV activity in both LFD and HFD. In HFD‐induced obesity, coupled with insulin desensitization, we found no favorable effect of succinic acid on glucose regulation, though adiposity was attenuated. In oxidative skeletal muscle, there was a tendency for increased respiratory capacity, likely owed to greater mitochondrial content, suggestive of a succinic acid‐induced mitochondrial biogenesis.

Molecular and Metabolic Mechanism of Low-Intensity Pulsed Ultrasound Improving Muscle Atrophy in Hindlimb Unloading Rats

“…Both 30 mW/cm 2 and 80 mW/cm 2 LIPUS significantly increased the serum L-alanine level of hind limb unloading rats. In this study, we found that succinic acid as a key metabolite affects the metabolic balance, which is similar to the results of skeletal muscle metabolic abnormality model, in which succinic acid was found to induced the biosynthesis of mitochondria, promote the increase of the number of mitochondria, and enhance the respiratory capacity of oxidative skeletal muscle, and proposed that the significant decrease of succinic acid content in hind limb unloading may be related to the biosynthesis [69].Aspartic acid plays a variety of functions in physiological and biological processes and is a non-essential amino acid in mammals [70].Aspartic acid is used for the biosynthesis of nucleotides and proteins, and also plays an important role in skeletal muscle metabolism [71]. For example, aspartic acid supplementation can regulate muscle glucose uptake and improve muscle utilization of excess fatty acids and glycogen in rats [72,73].…”

Amber Extract Reduces Lipid Content in Mature 3T3-L1 Adipocytes by Activating the Lipolysis Pathway

“…It is necessary to investigate the active components in amber extract, and our previous studies have attempted to identify the components using HPLC. Succinic acid, a major component of amber, has been reported to increase the production of heat by brown adipose tissue [ 21 ] and suppress lipid accumulation [ 22 ]. Recently, it has been reported that succinate accumulation in hypoxic adipose tissue contributes to lipolysis and insulin resistance [ 23 ], suggesting that exogenous succinic acid could promote lipolysis.…”

Life without Proteinase Activated Receptor 2 (PAR2) Alters Body Composition and Glucose Tolerance in Mice

“…Further, epididymal adipose tissue (EAT) mass was assessed in YG mice (n = 8) and a subset of AG (n = 6) and PAR2KO-AG (n = 8) mice. Though we have previously documented that EAT and NMR are highly related [ 15 ]. The remaining AG and PAR2KO-AG mice were not euthanized and used for a separate study.…”