Assessment of Pharmacology, Safety, and Metabolic activity of Capsaicin Feeding in Mice

Padmamalini Baskaran,Jonathan Fox,Liesl Zimmerman,Jane Bennis,Laurel Markert,Baskaran Thyagarajan

doi:10.1038/s41598-019-45050-0

Padmamalini Baskaran, Jonathan Fox + Show 4 more

Open Access

https://doi.org/10.1038/s41598-019-45050-0

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Journal: Scientific Reports	Publication Date: Jun 13, 2019
Citations: 16	License type: open-access

Affiliation: University of Wyoming

Abstract

Capsaicin (CAP) activates transient receptor potential vanilloid subfamily 1 (TRPV1) to counter high-fat diet (HFD)-induced obesity. Several studies suggest that CAP induces the browning of white adipocytes in vitro or inguinal white adipose tissue (iWAT) in vivo. However, there is a lack of data on the dose-response for CAP to inhibit HFD-induced obesity. Therefore, we first performed experiments to correlate the effect of various doses of CAP to prevent HFD-induced weight gain in wild-type (WT) mice. Next, we performed a subchronic safety study in WT mice fed a normal chow diet (NCD ± CAP, 0.01% in NCD) or HFD ± CAP (0.01% in HFD) for eight months. We analyzed the expression of adipogenic and thermogenic genes and proteins in the iWAT from these mice, conducted histological studies of vital organs, measured the inflammatory cytokines in plasma and iWAT, and evaluated liver and kidney functions. The dose-response study showed that CAP, at doses above 0.001% in HFD, countered HFD-induced obesity in mice. However, no difference in the anti-obesity effect of CAP was observed at doses above 0.003% in HFD. Also, CAP, above 0.001%, enhanced the expression of sirtuin-1 and thermogenic uncoupling protein 1 (UCP-1) in the iWAT. Safety analyses suggest that CAP did not cause inflammation. However, HFD elevated plasma alanine aminotransferase and creatinine, caused iWAT hypertrophy and hepatic steatosis, and CAP reversed these. Our data suggest that CAP antagonizes HFD-induced metabolic stress and inflammation, while it does not cause any systemic toxicities and is well tolerated by mice.

Highlights

Since there is lack of data on the pharmacological effect of oral feeding of various doses of pure CAP and its long-term safety in mice, we performed a dose response study and 8-month subchronic safety analyses by feeding mice with pure CAP either in normal chow diet (NCD) or highfat diet (HFD) (60% calories from fat)
To establish a correlation between various doses of CAP and inhibition of HFD (60% calories from fat)-induced obesity, we fed wild type (WT) mice (8 mice/ group) a HFD (± 0.001%, 0.003%, 0.005%, 0.01% or 0.03% of CAP, which correspond to a 0.133 mg/kg, 0.399 mg/kg, 0.665 mg/kg, 1.33 mg/kg and 3.99 mg/kg body weight) for 32 weeks
Since previous studies have not evaluated the effect of long-term feeding of CAP at the dose or 0.01% in NCD, we fed mice either NCD or NCD (±0.01 CAP) for 32 weeks, isolated the inguinal WAT at the end of 32 weeks to analyze the expression of thermogenic uncoupling protein 1 (UCP-1) and SiRT-1

Summary

Introduction

Since there is lack of data on the pharmacological effect of oral feeding of various doses of pure CAP (not as red pepper powder, chili powder, its derivative, capsaicinoids or capsinoids) and its long-term safety in mice, we performed a dose response study and 8-month subchronic safety analyses by feeding mice with pure CAP either in normal chow diet (NCD) or HFD (60% calories from fat). We evaluated the effect of feeding 0.01% CAP in NCD in the WT mice and determined the body weight gain, energy intake and metabolic activity. Since previous studies have not evaluated the effect of long-term feeding of CAP at the dose or 0.01% in NCD, we fed mice either NCD or NCD (±0.01 CAP) for 32 weeks, isolated the inguinal WAT at the end of 32 weeks to analyze the expression of thermogenic UCP-1 and SiRT-1.

Results

Conclusion