Immunomodulatory Role of an Ayurvedic Formulation on Imbalanced Immunometabolics during Inflammatory Responses of Obesity and Prediabetic Disease

Kal-1 is a polyherbal decoction of seven different natural ingredients, traditionally used in controlling sugar levels, inflammatory conditions particularly regulating metabolic and immunoinflammatory balance which are the major factors involved in obesity and related diseases. In the present study, we aimed to investigate the effect of Kal-1 (an abbreviation derived from the procuring source) on diet-induced obesity and type II diabetes using C57BL/6J mice as a model. The present study was performed with two experimental groups involving obese and prediabetic mice as study animals. In one, the mice were fed on high-fat with increased sucrose diet, and different amounts (5, 20, and 75 μL) of Kal-1 were administered with monitoring of disease progression over a period of 21 weeks whereas in the second group the mice were first put on the same diet for 21 weeks and then treated with the same amounts of Kal-1. A significant reduction in body weight, fat pads, fasting blood glucose levels, insulin levels, biochemical parameters, immunological parameters, and an array of pro- and anticytokines was observed in obese and diabetic mice plus Kal-1 than control (lean) mice fed on normal diet. In conclusion, Kal-1 has immunomodulatory potential for diet-induced obesity and associated metabolic disorders.

[1]  M. Zemel Mechanisms of dairy modulation of adiposity. , 2003, The Journal of nutrition.

[2]  I. G. Fantus,et al.  Curcumin Prevents High Fat Diet Induced Insulin Resistance and Obesity via Attenuating Lipogenesis in Liver and Inflammatory Pathway in Adipocytes , 2012, PloS one.

[3]  M. Heo,et al.  Determinants of leptin gene expression in fat depots of lean mice. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[4]  J. Friedman,et al.  Identification of White Adipocyte Progenitor Cells In Vivo , 2008, Cell.

[5]  Y. Zick,et al.  Role of Ser/Thr kinases in the uncoupling of insulin signaling , 2003, International Journal of Obesity.

[6]  G. Matarese,et al.  The weight of leptin in immunity , 2004, Nature Reviews Immunology.

[7]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[8]  P. Trayhurn Adipocyte biology , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[9]  N. Al-Daghri,et al.  Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians , 2006, Cardiovascular diabetology.

[10]  Y. Matsuzawa The metabolic syndrome and adipocytokines , 2006, Expert review of clinical immunology.

[11]  S. Coppack Pro-inflammatory cytokines and adipose tissue , 2001, Proceedings of the Nutrition Society.

[12]  G. Fantuzzi Adipose tissue, adipokines, and inflammation. , 2005, The Journal of allergy and clinical immunology.

[13]  Herbert Tilg,et al.  Adipocytokines: mediators linking adipose tissue, inflammation and immunity , 2006, Nature Reviews Immunology.

[14]  J. Bełtowski Adiponectin and resistin--new hormones of white adipose tissue. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[15]  O. MacDougald,et al.  Adipocyte differentiation from the inside out , 2006, Nature Reviews Molecular Cell Biology.

[16]  E J Freireich,et al.  Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. , 1966, Cancer chemotherapy reports.

[17]  Roger J. R. Levesque,et al.  Obesity and Overweight , 2011 .

[18]  K. Fallon,et al.  The acute phase response and exercise: court and field sports , 2001, British journal of sports medicine.

[19]  J. Rankin,et al.  Inflammatory Response to a High‐fat, Low‐carbohydrate Weight Loss Diet: Effect of Antioxidants , 2008, Obesity.

[20]  M. Honda,et al.  A liver-derived secretory protein, selenoprotein P, causes insulin resistance. , 2010, Cell metabolism.

[21]  S. Tangye,et al.  Inflammatory Mechanisms in Obesity , 2013 .

[22]  C. Dolea,et al.  World Health Organization , 1949, International Organization.

[23]  M. Lazar,et al.  Resistin and obesity-associated insulin resistance , 2002, Trends in Endocrinology & Metabolism.

[24]  A. Eberle,et al.  LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha in human adipocytes. , 2008, Cytokine.

[25]  L. Howard,et al.  Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet. , 2009, Molecular nutrition & food research.

[26]  C. Kahn Can We Nip Obesity in Its Vascular Bud? , 2008, Science.

[27]  H. Tilg,et al.  Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. , 2004, Biochemical and biophysical research communications.

[28]  Laura Herrero,et al.  Obesity, inflammation, and insulin resistance. , 2007, Gastroenterology.

[29]  S. Zolotukhin,et al.  Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Michael Müller,et al.  A saturated fatty acid-rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. , 2009, The American journal of clinical nutrition.

[31]  T. Kadowaki,et al.  Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance* , 2006, Journal of Biological Chemistry.

[32]  J. Hebebrand,et al.  [Obesity and overweight]. , 2009, Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie.

[33]  P. Cryer,et al.  Effect of short-term fasting on lipid kinetics in lean and obese women. , 1999, American journal of physiology. Endocrinology and metabolism.

[34]  R. Leibel,et al.  The role of leptin in human physiology. , 1999, The New England journal of medicine.

[35]  S. Han,et al.  Diet-induced obesity leads to decreased hepatic iron storage in mice. , 2011, Nutrition research.

[36]  C. Meier,et al.  Adipose tissue: a regulator of inflammation. , 2005, Best practice & research. Clinical endocrinology & metabolism.

[37]  S. Klaus Functional differentiation of white and brown adipocytes , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[38]  K. Kristiansen,et al.  Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice , 2011, PloS one.

[39]  R. Yu,et al.  Mesenteric Adipose Tissue‐Derived Monocyte Chemoattractant Protein‐1 Plays a Crucial Role in Adipose Tissue Macrophage Migration and Activation in Obese Mice , 2006, Obesity.

[40]  A. Papavassiliou,et al.  Nrf2 Represses FGF21 During Long-Term High-Fat Diet–Induced Obesity in Mice , 2011, Diabetes.