Diosgenin Supplementation Prevents Lipid Accumulation and Induces Skeletal Muscle-Fiber Hypertrophy in Rats

Abstract

Diosgenin (Dio) is a steroid sapogenin found in plants such as Dioscorea species, and is recognized as a phytochemical against various disorders as well as a natural precursor of steroidal drugs. The present study used rats fed high-cholesterol (Chol) diets supplemented with or without 0.5% Dio for 6 wk to investigate the effects of dietary Dio on lipid metabolism. Dio supplementation significantly increased serum high-density lipoprotein Chol concentrations and fecal Chol content, and significantly decreased fecal bile acid content compared rats fed a high-Chol diet alone, showing that dietary Dio may facilitate excretion of Chol rather than bile acids. A reduction in the liver triglyceride content and intra-abdominal visceral fat was observed in Dio-supplemented rats. Interestingly, dietary Dio also significantly increased the skeletal muscle-fiber diameter and area in the thigh muscles of the rats. Mouse myoblast-derived C2C12 cells were used to examine whether Dio directly affected skeletal muscle. Dio promoted fusion of myoblasts into multinucleated cells or myotubes. Furthermore, in myotube C2C12 cells, protein levels of phosphorylated AMPactivated protein kinase (AMPK) increased with Dio treatment in a dose-dependent manner. These results indicate that Dio may not only induce myoblast fusion and enhance skeletal muscle as an energy expenditure organ, but may also activate the catabolic pathway via AMPK in skeletal muscle cells. Thus, these effects of Dio on skeletal muscles may contribute to inhibition of visceral fat accumulation. Key Words dietary supplements, lipid metabolism, cholesterol, visceral fat, skeletal muscle, skeletal muscle cells, myoblast fusion, AMPK Diosgenin (Dio; Pubchem ID 99474) is a steroid sapogenin found in plants such as Dioscorea, Trigonella, Costus, and Smilax species, and is a constituent of the saponin, dioscin, which is found in the rootstock of yam (Dioscorea) (1, 2). Dio is a natural precursor of steroidal drugs, including sex hormones and corticosteroids, indicating its importance in the pharmaceutical industry. Additionally, Dio itself has pharmacological potential and behaves as a biologically active phytochemical that is used in the treatment of various disorders, including inflammation, hypercholesterolemia, cancer, and several types of infections. Tohda et al. identified 1,25D3-membrane-associated, rapid response steroidbinding protein (1,25D3-MARRS) as a target protein of Dio and demonstrated that Dio induces axonal growth and regrowth of neurons as an exogenous stimulator of 1,25D3-MARRS, and may act on critical signaling path

Medicinal and edible plants in the treatment of dyslipidemia: advances and prospects

“…In Wistar rats fed with high-cholesterol diets, administration of 0.5% diosgenin for 6 weeks significantly increased serum HDL concentrations and fecal cholesterol contents, but decreased the levels of hepatic TC, TG and fecal bile acids. The potential lipid-lowering mechanism might be through activating the catabolic pathway of AMPK, thus inhibiting cholesterol absorption and facilitating cholesterol excretion [162]. Resistant starch is a component of starch that is not digested in the small intestine but fermented by the microbiota in colon and produces short-chain fatty acids [163].…”

Naringin Ameliorates Skeletal Muscle Atrophy and Improves Insulin Resistance in High-Fat-Diet-Induced Insulin Resistance in Obese Rats

“…However, muscle contractions depend on the number and size of the fibres [ 33 ]. The analysis of the muscle fibres was calculated by measuring the CSA, and the diameter [ 27 ]. These results showed that the HFD group had a decreased diameter, and CSA in their skeletal muscles, which led to muscle fibre atrophy, when compared to the control group.…”

“…These results showed that the HFD group had a decreased diameter, and CSA in their skeletal muscles, which led to muscle fibre atrophy, when compared to the control group. Previous studies showed that the high-fat-diet-fed rats CSA, number of fibres, and diameters of their soleus and quadriceps had decreased, which led to reduced muscle weight and also impaired force of muscle contraction [ 27 , 34 , 35 ]. Conversely, the skeletal muscle parameters from the histological analysis in our study of the naringin treatment were higher than both the HFD and the HFD + SIM groups.…”

“…In addition, each sample was labelled with a coding number, and the muscle histology of each rat was determined for three slides with five random areas per slide. The quadricep muscles were fixed in 10% neutral buffered formalin, cut into 5 µm thick sections, and then stained with H&E. The cross-section areas (CSA), and diameter (minimal Feret’s diameter) of muscle fibres per unit area were calculated in five random fields of each section, as previously described [ 20 , 27 ]. Images of the stained sections were obtained under a light microscope and measured using Image J software.…”

Diosgenin and Its Analogs: Potential Protective Agents Against Atherosclerosis

“…117 The cholesterol transport system not only inhibits the intestinal absorption of cholesterol but also carries cholesterol from peripheral tissues to the liver, excreting it into bile or forming free cholesterol, which is then excreted through the intestine to the body. 118 Diosgenin can promote fecal cholesterol excretion and inhibit cholesterol absorption in mice and rats; 85,107,119 this effect is related to Niemann-Pick C1-Like 1 (NPC1L1) and ATP-binding cassette G5/8(ABCG5/8). NPC1L1 is a transmembrane protein highly expressed in the intestine and liver, which mediates the excretion of intestinal sterols and hepatic cholesterol.…”