Chitosan is a natural product derived from chitin. To investigate the hypoglycemic and anti-obesity effects of chitosan, male Sprague–Dawley rats were divided into four groups: normal control, diabetic, and diabetic fed 5% or 7% chitosan. Diabetes was induced in rats by injecting streptozotocin/nicotinamide. After 10 weeks of feeding, the elevated plasma glucose, tumor necrosis factor-α, and interleukin-6 and lower adiponetin levels caused by diabetes were effectively reversed by chitosan treatment. In addition, 7% chitosan feeding also elevated plasma glucagon-like peptide-1 levels and lowered the insulin resistance index (homeostasis model assessment) in diabetic rats. Lower adipocyte granular intensities and higher lipolysis rates in adipose tissues were noted in the 7% chitosan group. Moreover, chitosan feeding reduced hepatic triglyceride and cholesterol contents and increased hepatic peroxisomal proliferator-activated receptor α expression in diabetic rats. Our results indicate that long-term administration of chitosan may reduce insulin resistance through suppression of lipid accumulation in liver and adipose tissues and amelioration of chronic inflammation in diabetic rats.
Get full access to this article
View all access options for this article.
References
1.
OrbanZ, RemaleyAT, SampsonM, TrajanoskiZ, ChrousosGP. The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man. J Clin Endocrinol Metab, 1999; 84:2126–2133.
2.
GuilhermeA, VirbasiusJV, PuriV, CzechMP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol, 2008; 9:367–377.
3.
BloomgardenZT. Adiposity and diabetes. Diabetes Care, 2002; 25:2342–2349.
4.
MenzaghiC, TrischittaV, DoriaA. Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes, 2007; 56:1198–1209.
5.
Guerre-MilloM, RouaultC, PoulainP. PPAR-alpha null mice are protected from high-fat diet-induced insulin resistance. Diabetes, 2001; 50:2809–2814.
IdeT, NakazawaT, MochizukiT, MurakamiK. Tissue-specific actions of antidiabetic thiazolidinediones on the reduced fatty acid oxidation in skeletal muscle and liver of Zucker diabetic fatty rats. Metabolism, 2000; 49:521–525.
KimH, HaluzikM, AsgharZ. Peroxisome proliferator-activated receptor α agonist treatment in a transgenic model of type 2 diabetes reserves the lipotoxic state and improves glucose homeostasis. Diabetes, 2003; 52:1770–1778.
10.
KiefferTJ, HabenerJF. The glucagon-like peptides. Endocr Rev, 1999; 20:876–913.
11.
DruckerDJ. The biology of incretin hormones. Cell Metab, 2006; 3:153–165.
12.
Toft-NielsenMB, DamholtMB, MadsbadS. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab, 2001; 86:3717–3723.
13.
DelzenneNM, CaniPD, DaubioulC, NeyrinckAM. Impact of inulin and oligofructose on gastrointestinal peptides. Br J Nutr, 2005; 93,Suppl 1:S157–S161.
14.
ZhouJ, MartinRJ, TulleyRTet al.Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab, 2008; 295:E1160–E1166.
15.
PapathanasopoulosA, CamilleriM. Dietary fiber supplements: effects in obesity and metabolic syndrome and relationship to gastrointestinal functions. Gastroenterology, 2010; 138:65–72.
HanLK, KimuraY, OkudaH. Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet. Int J Obes Relat Metab Disord, 1999; 23:174–179.
24.
SumiyoshiM, KimuraY. Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice. J Pharm Pharmacol, 2006; 58:201–207.
25.
YaoHT, HuangSY, ChiangMT. A comparative study on hypoglycemic and hypocholesterolemic effects of high and low molecular weight chitosan in streptozotocin-induced diabetic rats. Food Chem Toxicol, 2008; 46:1525–1534.
26.
BergerJJ, BarnardRJ. Effect of diet on fat cell size and hormone-sensitive lipase activity. J Appl Physiol, 1999; 87:227–232.
27.
MuraseT, YamadaN, MatsuzakiF. The in vitro effect of growth hormone on adipose tissue lipoprotein lipase in rats. Life Sci, 1981; 28:199–201.
28.
FolchJ, LeesM, Sloane-StanleyGM. A purification of total lipid from animal tissue. J Biol Chem, 1957; 226:497–509.
MaroniBJ, HaesemeyerR, WilsonLK, DiGirolamoM. Electronic determination of size and number in isolated unfixed adipocyte populations. J Lipid Res, 1990; 31:1703–1709.
31.
Hernández-GonzálezSO, González-OrtizM, Martínez-AbundisEet al.Chitosan improves insulin sensitivity as determined by the euglycemic-hyperinsulinemic clamp technique in obese subjects. Nutr Res, 2010; 30:392–395.
32.
MatsuzawaY. The metabolic syndrome and adipocytokines. FEBS Lett, 2006; 580:2917–2921.
33.
HotamisligilGS, ShargillNS, SpiegelmanBM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 1993; 259:87–91.
34.
BastardJP, MaachiM, Van-NhieuJTet al.Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab, 2002; 87:2084–2089.
35.
NeyrinckAM, BindelsLB, De BackerFet al.Dietary supplementation with chitosan derived from mushrooms changes adipocytokine profile in diet-induced obese mice, a phenomenon linked to its lipid-lowering action. Int Immunopharmacol, 2009; 9:767–773.
36.
SuganoM, FujikawaT, HiratsujiY, NakashimaK, FukudaN, HasegawaY. A novel use of chitosan as a hypocholesterolemic agent in rats. Am J Clin Nutr, 1980; 33:787–793.
37.
SumiyoshiM, KimuraY. Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice. J Pharm Pharmacol, 2006; 58:201–207.
38.
GallaherCM, MunionJ, HesslinkRJr, WiseJet al.Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr, 2000; 11:2753–2759.
39.
YaoHT, ChiangMT. Effect of chitosan on plasma lipids, hepatic lipids, and fecal bile acid in hamsters. J Food Drug Anal, 2006; 14:183–189.
40.
GutzwillerJP, DreweJ, GokeBet al.Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol, 1999; 276:R1541–R1544.
41.
Van-DijkG, ThieleTE. Glucagon-like peptide-1 (7–36) amide: a central regulator of satiety and interoceptive stress. Neuropeptides, 1999; 33:406–414.
42.
OkudaH, MorimotoC, TsujitaT. Effect of substrates on the cyclic AMP-dependent lipolytic reaction of hormone-sensitive lipase. J Lipid Res, 1994; 35:1267–1273.
ZechnerR. The tissue-specific expression of lipoprotein lipase: implications for energy and lipoprotein metabolism. Curr Opin Lipidol, 1997; 8:77–88.
45.
ZechnerR, StraussJ, FrankSet al.The role of lipoprotein lipase in adipose tissue development and metabolism. Int J Obes Relat Metab Disord, 2000; 24,Suppl 4:S53–S56.
46.
LeeYS, ShinS, ShigiharaTet al.Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis. Diabetes, 2007; 56:1671–1679.
47.
MatsuoK, AraiH, MutoKet al.The anti-obesity effect of the palatinose-based formula inslow is likely due to an increase in the hepatic PPAR-alpha and adipocyte PPAR-gamma gene expressions. J Clin Biochem Nutr, 2007; 40:234–241.
