Abstract
Methylsulfonylmethane (MSM), an organosulfur compound, has been used as a dietary
supplement that can improve various metabolic diseases. However, the effect of MSM
on obesity-linked metabolic disorders remains unclear. The goal of the current study
is to determine whether MSM has beneficial effects on glucose and lipid homeostasis
in obesity-associated pathophysiologic states. High-fat diet-induced obese (DIO) and
genetically obese diabetic db/db mice treated with MSM (1%–5% v/v, by drinking water) were studied. Metabolic parameters involved in glucose and lipid
metabolism were determined. Treatment of DIO mice with MSM leads to a significant
decrease in blood glucose levels. DIO mice treated with MSM are hypersensitive to
insulin, as evidenced by decreased serum insulin and an increase in the area above
the curve during an ITT. Concurrently, MSM reduces hepatic triglyceride and cholesterol
contents in DIO mice. These effects are accompanied by reductions in gene expression
of key molecules involved in lipogenesis and inflammation. FACS analysis reveals that
MSM markedly increases the frequency of B cells and decreases the frequency of myeloid
cells in peripheral blood and in bone marrow. Moreover, overnutrition-induced changes
of femur microarchitecture are restored by MSM. In db/db mice, a marked impairment
in glucose and lipid metabolic profiles is notably ameliorated when MSM is supplemented.
These data suggest that MSM has beneficial effects on multiple metabolic dysfunctions,
including hyperglycemia, hyperinsulinemia, insulin resistance, and inflammation. Thus,
MSM could be the therapeutic option for the treatment of obesity-related metabolic
disorders such as type 2 diabetes and fatty liver diseases.
Keywords
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References
- Obesity and diabetes in the developing world—a growing challenge.N Engl J Med. 2007; 356: 213-215
- Obesity, inflammation, and the gut microbiota.Lancet Diabetes Endocrinol. 2015; 3: 207-215
- Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?.Diabetes. 2015; 64: 1886-1897
- Obesity-driven disruption of haematopoiesis and the bone marrow niche.Nat Rev Endocrinol. 2014; 10: 737-748
- Altern Med Rev. 2003; 8: 438-441
- Targeted disruption of ROCK1 causes insulin resistance in vivo.J Biol Chem. 2009; 284: 11776-11780
- Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis.Clin Drug Investig. 2004; 24: 353-363
- Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets.Diabetes Metab Res Rev. 2009; 25: 370-379
- Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet.Br J Nutr. 2015; : 1-9
- Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels.Mol Metab. 2014; 3: 565-580
- Role of sulfur containing amino acids as an adjuvant therapy in the prevention of diabetes and its associated complications.Curr Diabetes Rev. 2013; 9: 237-248
- Sulfur amino acids in diet-induced fatty liver: a new perspective based on recent findings.Molecules. 2014; 19: 8334-8349
- Supplementation with methyl donors during lactation to high-fat-sucrose-fed dams protects offspring against liver fat accumulation when consuming an obesogenic diet.J Dev Orig Health Dis. 2014; : 1-11
- Ulcers caused by bullous morphea: successful therapy with N-acetylcysteine and topical wound care.Int J Immunopathol Pharmacol. 2013; 26: 259-262
- Accelerated wound healing by S-methylmethionine sulfonium: evidence of dermal fibroblast activation via the ERK1/2 pathway.Pharmacology. 2010; 85: 68-76
- The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages.Biol Pharm Bull. 2009; 32: 651-656
- Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice.Inflammation. 2013; 36: 1111-1121
- Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis.World J Hepatol. 2014; 27: 98-106
- Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats.Arch Pharm Res. 2013; 36: 1140-1148
- Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model.J Bone Miner Metab. 2013; 31: 16-25
- Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: randomized trial.Int J Immunopathol Pharmacol. 2016; 29: 140-146
- Methylsulfonylmethane inhibits NLRP3 inflammasome activation.Cytokine. 2015; 71: 223-231
- Hepatic nuclear corepressor 1 regulates cholesterol absorption through a TRbeta1-governed pathway.J Clin Invest. 2014; 124: 1976-1986
- ROCK1 isoform-specific deletion reveals a role for diet-induced insulin resistance.Am J Physiol Endocrinol Metab. 2013; 306: E332-E343
- Role of rho-kinase in regulation of insulin action and glucose homeostasis.Cell Metab. 2005; 2: 119-129
- The therapeutic potential of nuclear receptor modulators for treatment of metabolic disorders: PPARgamma, RORs, and rev-erbs.Cell Metab. 2014; 19: 193-208
- Rosiglitazone, PPARgamma, and type 2 diabetes.N Engl J Med. 2010; 363: 2667-2669
- Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.N Engl J Med. 2007; 356: 2457-2471
- Thiazolidinediones and PPARgamma agonists: time for a reassessment.Trends Endocrinol Metab. 2012; 23: 205-215
- Effects of diabetes drugs on the skeleton.Bone. 2016; 82: 93-100
- Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes.Eur Heart J. 2015; 36: 2288-2296
- T2384, a novel antidiabetic agent with unique peroxisome proliferator-activated receptor gamma binding properties.J Biol Chem. 2008; 283: 9168-9176
- Pharmacological characteristics of a novel nonthiazolidinedione insulin sensitizer, FK614.Eur J Pharmacol. 2004; 494: 273-281
- PAR-1622 is a selective peroxisome proliferator-activated receptor gamma partial activator with preserved antidiabetic efficacy and broader safety profile for fluid retention.Arch Pharm Res. 2009; 32: 721-727
- Selective PPARgamma modulator INT131 normalizes insulin signaling defects and improves bone mass in diet-induced obese mice.Am J Physiol Endocrinol Metab. 2012; 302: E552-E560
- Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome.Lancet Diabetes Endocrinol. 2014; 2: 901-910
- Dimethyl sulphoxide and dimethyl sulphone are potent inhibitors of IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2.Life Sci. 2011; 89: 473-478
- Methylsulfonylmethane modulates apoptosis of LPS/IFN-gamma-activated RAW 264.7 macrophage-like cells by targeting p53, Bax, Bcl-2, cytochrome c and PARP proteins.Immunopharmacol Immunotoxicol. 2014; 36: 379-389
- The effect of methylsulfonylmethane on the experimental colitis in the rat.Toxicol Appl Pharmacol. 2011; 253: 197-202
- Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.Osteoarthritis Cartilage. 2006; 14: 286-294
- An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy.Diabetologia. 2013; 56: 1856-1866
- DNA methylation and hepatic insulin resistance and steatosis.Curr Opin Clin Nutr Metab Care. 2012; 15: 350-356
- Dysregulated hepatic methionine metabolism drives homocysteine elevation in diet-induced nonalcoholic fatty liver disease.PLoS One. 2015; 10 ([eCollection 2015]): e0136822https://doi.org/10.1371/journal.pone.0136822
- The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway.Nutrients. 2013; 5: 3481-3495
- S-adenosylmethionine metabolism and liver disease.Ann Hepatol. 2013; 12: 183-189
- Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulometric electrochemical detection: alterations with plasma homocysteine and pyridoxal 5'-phosphate concentrations.Clin Chem. 2000; 46: 265-272
- Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels.J Clin Endocrinol Metab. 2015; 100: E1491-E1501https://doi.org/10.1210/jc.2015-3204
- The effect of troglitazone on plasma homocysteine, hepatic and red blood cell S-adenosyl methionine, and S-adenosyl homocysteine and enzymes in homocysteine metabolism in Zucker rats.Metabolism. 2002; 51: 783-786
- Increased bone resorption and impaired bone microarchitecture in short-term and extended high-fat diet-induced obesity.Metabolism. 2011; 60: 243-249
- High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity.Mol Cell Endocrinol. 2015; 410: 35-41
- Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation.J Clin Invest. 2014; 124: 1-13
- Impact of an obesogenic diet program on bone densitometry, micro architecture and metabolism in male rat.Lipids Health Dis. 2012; 11: 91
- Effects of diet type and supplementation of glucosamine, chondroitin, and MSM on body composition, functional status, and markers of health in women with knee osteoarthritis initiating a resistance-based exercise and weight loss program.J Int Soc Sports Nutr. 2011; 8: 8
Article info
Publication history
Published online: July 20, 2016
Accepted:
July 14,
2016
Received:
March 28,
2016
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
