Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice
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Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.
Abstract
Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.
참고문헌 (33)
- Rajala MW, "Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis", Endocrinology, 144, pp.3765~3773 (2003)
- Wellen KE, "Inflammation, stress, and diabetes", J Clin Invest, 115, pp.1111~1119 (2005)
- Weisberg SP, "Obesity is associated with macrophage accumulation in adipose tissue", J Clin Invest, 112, pp.1796~1808 (2003)
- Xu H, "Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance", J Clin Invest, 112, pp.1821~1830 (2003)
- Hardie DG, "The AMP-activated protein kinase-fuel gauge of the mammalian cell", Eur J Biochem, 246, pp.259~273 (1997)
- Sag D, "Adenosine 5’-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype", J Immunol, 181, pp.8633~8641 (2008)
- Makinde AO, "Upregulation of 5’-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit", Circ Res, 80, pp.482~489 (1997)
- Zong H, "AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation", Proc Natl Acad Sci U S A, 99, pp.15983~15987 (2002)
- Ju JS, "Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase", Am J Physiol Cell Physiol, 292, pp.C564~C572 (2007)
- Iglesias MA, "AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats", Diabetes, 51, pp.2886~2894 (2002)
- 신은주, "Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice", Immune Network, 11(1), pp.59~67 (2011), 대한면역학회
- Steppan CM, "The hormone resistin links obesity to diabetes", Nature, 409, pp.307~312 (2001)
- Yang Q, "Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes", Nature, 436, pp.356~362 (2005)
- Olefsky JM, "Macrophages, inflammation, and insulin resistance", Annu Rev Physiol, 72, pp.219~246 (2010)
- Mertzw W, "Relation of glucose tolerance factor to impaired intravenous glucose tolerance of rats on stock diets", Am J Physiol, 196, pp.614~618 (1959)
- Schwarz K, "Chromium(III) and the glucose tolerance factor", Arch Biochem Biophys, 85, pp.292~295 (1959)
- Anderson RA, "Recent advances in the clinical and biochemical effects of chromium deficiency", Prog Clin Biol Res, 380, pp.221~234 (1993)
- Mertz W, "Chromium in human nutrition: a review", J Nutr, 123, pp.626~633 (1993)
- Anderson RA, "Chromium, glucose intolerance and diabetes", J Am Coll Nutr, 17, pp.548~555 (1998)
- Kim K, "Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus", PHYTOMEDICINE, 16, pp.856~863, ELSEVIER GMBH
- Kyungjae KIM, "Down-Regulation of Adipogenesis and Hyperglycemia in Diet-Induced Obesity Mouse Model by Aloe QDM", 응용약물학회지, 18(3), pp.336~342 (2010), 한국응용약물학회
- Jung-Ok Kim, "Antihyperglycemic and Antioxidative Effects of New Herbal Formula in Streptozotocin-Induced Diabetic Rats", Journal of Medicinal Food, 12(4), pp.728~735 (2009), 한국식품영양과학회
- Martín-Fuentes P, "Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response", J Immunol, 179, pp.3242~3248 (2007)
- Sahoo D, "The role of scavenger receptors in signaling, inflammation and atherosclerosis", Biochemistry of Atherosclerosis, 1, pp.70~91 (2006)
- Peiser L, "The function of scavenger receptors expressed by macrophages and their role in the regulation of inflammation", Microbes Infect, 3, pp.149~159 (2001)
- Stewart CR, "CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer", Nat Immunol, 11, pp.155~161 (2010)
- Hoebe K, "CD36 is a sensor of diacylglycerides", Nature, 433, pp.523~527 (2005)
- Stuart LM, "Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain", J Cell Biol, 170, pp.477~485 (2005)
- Shi H, "TLR4 links innate immunity and fatty acid-induced insulin resistance", J Clin Invest, 116, pp.3015~3025 (2006)
- Tsukumo DM, "Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance", Diabetes, 56, pp.1986~1998 (2007)
- Regazzetti C, "Hypoxia decreases insulin signaling pathways in adipocytes", Diabetes, 58, pp.95~103 (2009)
- Trayhurn P, "Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity", Br J Nutr, 100, pp.227~235 (2008)
- Cancello R, "Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss", Diabetes, 54, pp.2277~2286 (2005)