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Capsaicin but not Genistein Influences Modulation of Lipid Parameters by Obestatin in DIO-C57BL/6 Mice

  • Musunuru Suneel Kumar Reddy
  • Uma V. ManjapparaEmail author
Article
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Abstract

Capsaicin from chillies and genistein from soya bean have been shown to reduce cholesterol and triglyceride levels effectively. This study was done to test the hypothesis if these nutraceuticals could enhance reduction in body weight in combination with a satiety peptide namely obestatin produced in the stomach. It brings about satiety mainly by reducing jejunal motility by signalling through the hypothalamus. Significant reduction in food intake and moderate reduction in gain in body weight was observed upon intraperitoneal administration in rodents. We aimed to explore if co-administration with capsaicin or genistein could further enhance the ability of obestatin to reduce gain in body weight in Diet-Induced-Obese mice. After 18 weeks on high fat diet, 22-week-old C57BL/6 mice were randomly grouped, 6 mice in each group with an average weight of 44 ± 3 g. 0.5 mg/kgBW capsaicin, 2 mg/kgBW genistein, 160 nmol/kgBW obestatin in 20% DMSO-saline was administered either individually or pairwise with obestatin, at the same time every day for a period of 8 days. Co-administration of obestatin and capsaicin showed increased reduction in food intake, gain in body weight, plasma and adipose triglycerides. Whereas, co-administration with genistein showed no enhanced effect on the parameters studied. mRNA profiling and western blot analysis of epididymal adipose tissue revealed upregulation of peroxisome proliferator-activated protein γ and DiacylGlycerol AcylTransferase1 by capsaicin + obestatin and adipose triglyceride lipase by capsaicin. This opens up the possibility of using multi-pronged approaches to counter obesity through food.

Keywords

Capsaicin Obesity Obestatin Epidydimal fat C57BL/6 mice 

Abbreviations

DIO

Diet induced obesity

HFD

High fat diet

BW

Body weight

TG

Triglyceride

TC

Total cholesterol

HDL-C

High density lipoprotein-cholesterol

ALP

Alkaline phosphatase

AST

Aspartate transaminase

ALT

Alanine transaminase

OB + GEN

Obestatin + genistein

OB + CAP

Obestatin + capsaicin

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

SREBF1

Sterol regulatory element binding transcription factor 1

PPARγ

Peroxisome proliferator-activated receptor gamma

ACACA

Acetyl-CoA carboxylase alpha

DGAT1

Diacylglycerol O-acyltransferase 1

HSL

Hormone-sensitive lipase

FSAN

Fatty acid synthase

ATGL

Adipose triglyceride lipase

LPL

Lipoprotein lipase

Notes

Acknowledgements

This work was financially supported under the BSC-0202 (WELFO) project of CSIR-CFTRI, funded by the Council of Scientific & Industrial Research, India (CSIR). MSKR would like to acknowledge CSIR for providing fellowship (31/005(0514)/2012-EMR-1). Authors would like to acknowledge R.S Govardhan Singh for helping in manuscript preparation.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

10989_2019_9811_MOESM1_ESM.docx (3.3 mb)
Supplementary material 1 (DOCX 3361 KB)

References

  1. Baboota RK, Murtaza N, Jagtap S et al (2014) Capsaicin-induced transcriptional changes in hypothalamus and alterations in gut microbial count in high fat diet fed mice. J Nutr Biochem 25:893–902CrossRefGoogle Scholar
  2. Barak Y, Nelson MC, Ong ES et al (1999) PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 4:585–595CrossRefGoogle Scholar
  3. Behloul N, Wu G (2013) Genistein: a promising therapeutic agent for obesity and diabetes treatment. Eur J Pharmacol 698:31–38CrossRefGoogle Scholar
  4. Chandramohan C, Niklas M, Joel T et al (2017) Triglyceride synthesis by DGAT1 protects adipocytes from lipid-induced ER stress during lipolysis. Cell Metab 26:407–418CrossRefGoogle Scholar
  5. Cummings DE, Overduin J (2007) Gastrointestinal regulation of food intake. J Clin Invest 117:13–23CrossRefGoogle Scholar
  6. Diepvens K, Westerterp KR, Westerterp-Plantenga MS (2007) Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol 292:R77–R85CrossRefGoogle Scholar
  7. Dong X-Y, He J-M, Tang S-Q et al (2009) Is GPR39 the natural receptor of obestatin? Peptides 30:431–438CrossRefGoogle Scholar
  8. Folch J, Lees M, Sloane Steyanly GH (1969) A Simple method for isolation and purification of total lipides from animal tissues. J Biol Chem 4:273–279Google Scholar
  9. Greenway FL, Bray GA (2010) Combination drugs for treating obesity. Curr Diab Rep 10:108–115CrossRefGoogle Scholar
  10. Hsu C-L, Yen G-C (2007) Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. J Agric Food Chem 55:1730–1736CrossRefGoogle Scholar
  11. Kang J-H, Goto T, Han I-S, Kawada T et al (2010) Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity (Silver Spring) 18:780–787CrossRefGoogle Scholar
  12. Kawada T, Hagihara K, Iwai K (1986) Effects of capsaicin on lipid metabolism fed a high fat diet1 in rats. J Nutr 116:1272–1278CrossRefGoogle Scholar
  13. Kempaiah RK, Srinivasan K (2006) Beneficial influence of dietary curcumin, capsaicin and garlic on erythrocyte integrity in high-fat fed rats. J Nutr Biochem 17:471–478CrossRefGoogle Scholar
  14. Kim H, Nelson-dooley C, Della-fera MA et al (2006) Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr 136:409–414CrossRefGoogle Scholar
  15. Lee YM, Choi JS, Kim MH et al (2006) Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets. Nutrition 22:956–964CrossRefGoogle Scholar
  16. Moran TH, Dailey MJ (2009) Minireview: gut peptides: targets for antiobesity drug development? Endocrinology 150:2526–2530CrossRefGoogle Scholar
  17. Murakami K, Ide T, Nakazawa T et al (2001) Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to alpha and gamma isoforms of peroxisome-proliferator-activated receptors by competing with agonists. Biochem J 353:231–238CrossRefGoogle Scholar
  18. Nagaraj S, Manjappara UV (2016) Studies on the influence of CCK-8 on the ability of obestatin to reduce food intake, gain in body weight and related lipid parameters. Biochimie 125:126–130CrossRefGoogle Scholar
  19. Nagaraj S, Peddha MS, Manjappara UV (2008) Fragments of obestatin as modulators of feed intake, circulating lipids, and stored fat. Biochem Biophys Res Commun 366:731–737CrossRefGoogle Scholar
  20. Nagaraj S, Peddha MS, Manjappara UV (2009) Fragment analogs as better mimics of obestatin. Regul Pept 158:143–148CrossRefGoogle Scholar
  21. Nagaraj S, Raghavan AV, Rao SN, Manjappara UV (2014) Obestatin and Nt8U influence glycerolipid metabolism and PPAR gamma signaling in mice. Int J Biochem Cell Biol 53:414–422CrossRefGoogle Scholar
  22. Perry B, Wang Y (2012) Appetite regulation and weight control: the role of gut hormones. Nutr Diab 2:e26–e27CrossRefGoogle Scholar
  23. Rayalam S, Della-fera MA, Yang J et al (2007) Resveratrol potentiates Genistein’ s antiadipogenic and proapoptotic effects. J Nutr 2:2–7Google Scholar
  24. Rodgers RJ, Tschop MH, Wilding JPH (2012) Anti-obesity drugs: past, present and future. Dis Model Mech 5:621–626CrossRefGoogle Scholar
  25. Rosen ED, Sarraf, P, Troy AE et al (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4:611–617CrossRefGoogle Scholar
  26. Singh RSG, Manjappara UV (2016) Selective reduction of fat accumulation by soyasaponins A and B in high fat fed C57BL/6J mice. J Funct Foods 27:95–103CrossRefGoogle Scholar
  27. Spiegelman BM (1998) PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 47:507–514CrossRefGoogle Scholar
  28. Tan S, Gao B, Tao Y et al (2014) Antiobese effects of capsaicin—chitosan microsphere (CCMS) in obese rats induced by high fat diet. J Agric Food Chem 8:1866–1874CrossRefGoogle Scholar
  29. Troke RC, Tan TM, Bloom SR (2014) The future role of gut hormones in the treatment of obesity. Ther Adv Chronic Dis 5:4–14CrossRefGoogle Scholar
  30. WHO (2016) Obesity and overweight. Fact sheet (updated June 2016) of WHOGoogle Scholar
  31. Zhang JV, Ren P-G, Avsian-Kretchmer O et al (2005) Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 310:996–999CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Musunuru Suneel Kumar Reddy
    • 1
    • 2
  • Uma V. Manjappara
    • 1
    • 2
    Email author
  1. 1.Department of Lipid ScienceCSIR-Central Food Technological Research Institute (CFTRI)MysoreIndia
  2. 2.Academy of Scientific & Innovative ResearchCSIR-Central Food Technological Research Institute (CFTRI)MysoreIndia

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