Skip to main content
NCBI home page
Food Science and Biotechnology logoLink to Food Science and Biotechnology
. 2019 Dec 3;29(2):275–281. doi: 10.1007/s10068-019-00710-9

Red pepper seed water extract suppresses high-fat diet-induced obesity in C57BL/6 mice

Hwa-Jin Kim 1, Mi-Kyoung You 2, Ziyun Wang 3, Young-Hyeon Lee 3, Hyeon-A Kim 3,✉
PMCID: PMC6992834  PMID: 32064136

Abstract

In this study, the protective effect of red pepper seed water extract (RPS) against the obesity in high fat diet (HFD)-fed mice was investigated (HFD control group, and HFD group treated with 100 or 200 mg/kg body weight of RPS for 13 weeks). The application of RPS partially reversed the HFD-induced increases in body weight and adipose tissue weight. The patterns of the adipose tissue weights were parallel to the patterns of fat area, as measured in DXA procedure. In the adipose tissue, RPS suppressed the expression of adipogenic transcription factors and adipose marker genes. AMP-activated protein kinase activation was observed in the adipose tissue by RPS treatment. In addition, RPS improved high homeostasis model assessment of insulin resistance and hyperlipidemia in HFD fed mice. These findings suggest that RPS can be used as a potential therapeutic substance for reducing body fat and obesity related diseases.

Keywords: Red pepper seed, Anti-obesity, High-fat diet, HOMA-IR, Lipid metabolism

Introduction

It is widely acknowledged that excessive adipose tissue probably contributes to the development of obesity and other chronic diseases, such as diabetes, cancer, and atherosclerotic vascular disease (Barzilai and Gupta, 1999; Rosen and Spiegelman, 2014). Moreover, decreases in fat mass and its body distribution reduce the risk of chronic diseases and associated morbidity and mortality (Barzilai and Gupta, 1999; Hausman et al., 2001). Adipose tissue has an extraordinary ability to change its size and number. The growth of adipose tissue involves both cellular hypertrophy (increase in size) and hyperplasia (increase in number). Hypertrophy results from the accumulation of redundant lipids, while hyperplasia results from the occurrence of new adipocytes (Hausman et al., 2001; Rosen and Spiegelman, 2014).

Peppers (Capsicum annuum L.) have been used as traditional food pigment, spices, and external medicine from ancient times, and pepper seeds are the major waste products during the processing of peppers (Iorizz et al., 2002; Ki and Han, 2007; 2008; Song et al., 2010). Previous studies suggested that capsaicin accounts for the anti-obesity effect (Hsu and Yen, 2007; Lee et al., 2011). However, capsaicin is rarely contained in pepper seeds (Sim and Han, 2007). The inhibitory effects of defatted pepper seed extract (Sung et al., 2016b) and capsicoside G-rich fraction (Sung et al., 2016a) on HFD-induced obesity in mice have been demonstrated. However, fasting plasma lipids and blood glucose were not changed by the administration of capsicoside G-rich fraction in HFD-induced obese mice (Sung et al., 2016a; 2016b).

In our previous study, we confirmed the inhibitory effect of RPS on adipogenesis via AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes (Kim et al., 2018). Thus, in the present study, we focused on the potential negative effect of RPS on HFD-induced obese mice. We mainly sought to determine the effects of RPS on changes in body weight, food efficiency ratio (FER), and adipose tissue weight. We determined the levels of serum lipids and fasting blood glucose (FBG), which are related to obesity-induced chronic diseases. The expressions of the obesity-related transcription factors and enzymes in the adipose tissue were also examined to explore the underlying mechanism involved in its anti-obesity effect in the HFD-induced obese animal model.

Materials and methods

Preparation of RPS

The RPS was prepared according to the previous methods (Kim et al., 2018). In brief, red pepper seeds (200 g) were soaked in 1.8 L of water at 60 °C for 24 h. The extracts were centrifuged, filtered, evaporated, freeze-dried, and stored at − 70 °C until analysis. Icariside E5 and vanilloyl icariside E5 in our RPS were quantitatively analyzed as standard substances (Youn et al., 2017).

Animals

The animal studies were approved by the Institutional Animal Care and Use Committee of Mokpo National University (MNU-IACUC-2016-006). Five week old male C57BL/6 mice were obtained from Orient Co. (Seongnam-si, Gyeonggi-do, Republic of Korea). Mice were maintained under 22 ± 2 °C, 50 ± 10% relative humidity, and 12 h light/dark cycle, and had free access to diet and water. After 1 week’s acclimation, the mice were randomly divided into four groups: ND control group: ND-C, HFD control group: HFD-C, HFD group treated with 100 mg/kg body weight of RPS: HFD + RPS 100, HFD group treated with 200 mg/kg body weight of RPS: HFD + RPS 200. The ND was based on the AIN-93G diet from Research Diets Inc (New Brunswick, NJ, USA) containing 15.8% kcal fat, while the HFD contained 60% kcal fat (Table 1). The mice were administered distilled water (ND-C and HFD-C) or RPS by oral gavage once daily for 13 weeks. Changes in body weight of all mice were recorded weekly. To measure dual energy X-ray absorptiometry (DXA), the mice were anesthetized and put in the InAlyzer (MEDIOKRS Inc., Seongnam-si, Gyeonggi-do, Republic of Korea) with face downwards at week 12. After 13 weeks, blood was collected after 8 h fasting and serum was separated. Immediately following scarification of the mice, adipose tissue (visceral, intestinal, and epididymal) was removed, washed with PBS, weighed, and stored at − 70 °C for further analysis.

Table 1.

Composition of normal and high fat diet

Formulas
Classification Normal diet High fat diet
gm% kcal% gm% kcal%
Protein 20.0 20.3 26 20
Carbohydrate 64.0 63.9 26 20
Fat 7.0 15.8 35 60
Total 100.0 100
kcal/gm 3.9 5.24
Ingredient Normal diet High fat diet
gm kcal gm kcal
Casein 200 800.0 200 800
l-cystine 3 12 3 12
Corn starch 397 1590 0 0
Maltodextrin 132 528 125 500
Sucrose 100 400 68.8 275
Cellulose 50 0 50 0
Soybean oil 70 630 25 225
Lard 0 0 245 2205
t-Butylhydroquinone 0.014 0 0 0
Mineral mix S10022G 35 0 0 0
Mineral mix S10026G 0 0 10 0
DiCalcium phosphate 0 0 13 0
Calcium carbonate 0 0 5.5 0
Potassium citrate, 1 H2O 0 0 16.5 0
Vitamin mix V10001 0 0 10 40
Vitamin mix V10037 10 40 0 0
Choline bitrartrate 2.5 0 2 0
FD&C blue dye #1 0 0 0.05 0
Total 1000 4000 773.85 4057
Open in a new tab

Measurement of blood biochemical parameters

FBG and serum insulin concentrations were measured by using commercial kits (Allmedicus, Anyang-si, Gyeonggi-do, Republic of Korea and Shibayagi Co. Ltd., Gunma Pref., Japan, respectively). Serum lipids including triglyceride (TG), total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) were determined using an Automated Chemistry Analyzer (Beckman Coulter Inc., Brea, CA, USA) according to the manufacturer’s introductions. Homeostasis model assessment of insulin resistance (HOMA-IR) was expressed as FBG (mM) × insulin concentration (mU/L)/22.5 (Huang et al., 2002).

Western blot analysis

Tissues were homogenized in ice-cold radioimmune precipitation assay buffer (RIPA buffer, Thermo Fisher Scientific, Waltham, MA, USA) with 1% protease and phosphatase inhibitor cocktail. The cell lysates were centrifuged to collect the supernatant. Protein concentrations were determined using the Bradford (Sigma-Aldrich, St. Louis, MO, USA) method and equal amount of proteins (40 μg each) were separated on 10% SDS-PAGE gels and transferred onto a nitrocellulose membrane (Millipore, Billerica, MA, USA). The membranes were blocked for 1 h at 4 °C with 5% nonfat milk in Tris-buffered Saline and Tween 20 (TBST) buffer. The membranes were then incubated with primary antibodies [peroxisome proliferator-activated receptor (PPAR)-γ, fatty acid synthase (FAS), fatty acid-binding protein (FABP) 1, acetyl-CoA carboxylase (ACC), p-ACC, AMPK, and p-AMPK; Cell Signaling Technology, Beverly, MA, USA: CCAAT/enhancer-binding proteins (C/EBP) α, sterol regulatory element binding protein (SREBP)-1c, and β-actin; Santa Cruz Biotechnology Inc., Dallas, TX, USA] overnight and then with horseradish peroxidase-conjugated secondary antibodies [goat anti-rabbit or goat anti-mouse (1:2000)]. Bands were detected using the chemiluminescent substrate (IMGENEX, San Diego, CA, USA), and the protein expressions were quantified using UVP (imaging system for the chemiluminescent western blot, Upland, CA, USA) and Vision Works image (Analysis Software, Upland, CA, USA).

Statistical analysis

The statistical analyses were performed using SPSS 23.0 statistical program (SPSS Inc., Chicago, IL, USA). The data were determined using one-way analysis of variance (ANOVA) and followed by Duncan’s multiple comparisons test, where p values less than 0.05 were considered significant. Data are presented as mean ± SE.

Results and discussion

In our previous study, we observed the direct and profound inhibitory effects of RPS on the differentiation and accumulation of cellular lipids in 3T3-L1 adipocytes (Kim et al., 2018). In the present study, we sought to elucidate whether RPS could improve HFD-induced obesity, thereby improving important biomarkers of cardiovascular disease (CVD) including serum lipids and insulin sensitivity in C57BL/6 mice.

RPS suppresses HFD-induced increase in body weight, the adipose tissue weight and DXA image of fat content of mice

Several studies have already demonstrated that HFD can induce obesity in C57BL/6 mice (Choi et al., 2014; Jia et al., 2016; Lai et al., 2013; Wes et al., 1992). As shown in Fig. 1A, the HFD-C group showed a significantly higher weight gain versus the ND-C group. However, RPS supplementation partly decreased the weight gain in comparison with HFD-C group. Moreover, RPS treatment at 200 mg/kg remarkably reduced the weight gain up to 21.6% compared with HFD-C group (p = 0.01). This result is consistent with the findings of the researches which had demonstrated in vivo anti-obesity effect of capsicoside G-rich fraction (Sung et al., 2016a) and defatted pepper seed extract (Sung et al., 2016b).

Fig. 1.

Fig. 1

Open in a new tab

Effects of RPS on body weight gain, adipose tissue and DXA image of fat content in HFD-fed mice. (A) Body weight gain, (B) Adipose tissue weight and (C) Representative DXA image of fat content in mice. Means with the same letter represent values that are not significantly different based on one-way ANOVA followed by Duncan’s multiple range test (p < 0.05). ND: normal diet + distilled water, HFD: 60% high fat diet + distilled water, HFD + RPS 100: 60% high fat diet + red pepper seed extract 100 mg/kg, HFD + RPS 200: 60% high fat diet + red pepper seed extract 200 mg/kg

Compared with HFD-C group, the HFD + RPS 100 and 200 groups attenuated the total adipose tissue weight by 12.2% and 24.9%, respectively. Mice were treated with RPS suppressed the weight of the visceral and intestinal adipose tissues. Notably, HFD + RPS 200 group dramatically decreased the intestinal fat weight by 32.8%, leading to a level close to that of the ND-C group (Fig. 1B, p = 0.01). Furthermore, patterns of the adipose tissue weight were parallel to the patterns of fat area, as measured in DXA procedure. Similar to the effect on adipose tissue weight, DXA revealed that RPS at 200 mg/kg also decreased body fat (yellow and red color) compared with HFD-C group (Fig. 1C).

Although there were no significant differences in food intake among HFD groups (Fig. 2A), RPS-treated groups manifested a significant decrease in food efficiency ratio (FER) compared with HFD-C group (Fig. 2B). Based on this results, RPS did not suppressed body weight gain by reduced food intake.

Fig. 2.

Fig. 2

Open in a new tab

Effects of RPS on food intake FER in HFD-fed mice. (A) Food intake and (B) Food efficiency ratio. Means with the same letter represent values that are not significantly different based on one-way ANOVA followed by Duncan’s multiple range test (p < 0.05). ND: normal diet + distilled water, HFD: 60% high fat diet + distilled water, HFD + RPS 100: 60% high fat diet + red pepper seed extract 100 mg/kg, HFD + RPS 200: 60% high fat diet + red pepper seed extract 200 mg/kg

RPS regulates the expression of adipogenesis-related proteins in adipose tissue of HFD-fed mice

To assess the potential anti-obesity effect of RPS in adipose tissue further, the expressions of adipogenic transcription factors and adipose marker genes were measured. Among the adipogenesis-related transcription factors, PPAR-γ, C/EBP α, and SREBP-1c play key roles to determine the fate of adipogenesis, affecting the subsequent proteins, such as FAS, FABP4, and ACC (He et al., 2013; Lane et al., 1999; Li et al., 2016). HFD caused a significant upsurge of adipogenic transcription factors in the adipose tissue compared with the ND-C group, whereas RPS-treated groups markedly down-regulated the expression of PPAR-γ and C/EBP α (Fig. 3A). SREBP-1c expression showed a significant difference at 200 mg/kg of RPS (Fig. 3A). Interestingly, HFD + RPS 200 group dramatically suppressed the expression of PPAR-γ, C/EBP α, and SREBP-1c to a level similar to that in the ND-C group (p = 0.012, p = 0.004, p = 0.01, respectively).

Fig. 3.

Fig. 3

Open in a new tab

Effects of RPS on protein expression in the adipose tissue of HFD-fed mice. (A) transcription factors, (B) lipogenic enzymes, and (C) p-AMPK, AMPK and p-AMPK/AMPK ratio. Values are mean ± SE. Means with the same letter represent values that are not significantly different based on one-way ANOVA followed by Duncan’s multiple range test (p < 0.05). ND: normal diet + distilled water, HFD: 60% high fat diet + distilled water, HFD + RPS 100: 60% high fat diet + red pepper seed extract 100 mg/kg, HFD + RPS 200: 60% high fat diet + red pepper seed extract 200 mg/kg

In addition, high dose of RPS (200 mg/kg) reversed the increase in FAS and FABP4 expression caused by HFD (Fig. 3B). Furthermore, HFD + RPS 200 group significantly up-regulated p-ACC/ACC expression compared with that of the HFD-C group (Fig. 3B, p = 0.021). FAS, FABP4, and ACC, the critical adipose marker genes, are associated with fatty acids and TG synthesis (He et al., 2013). These data confirmed that RPS alleviated HFD-induced obesity partially via suppression of adipose marker genes.

In our previous study, Compound C, which is a known inhibitor of AMPK, partially reversed the lipid-lowering effect of RPS (Kim et al., 2018). Based on our observations that RPS increased AMPK phosphorylation in 3T3-L1 cells (Kim et al., 2018), we assessed the expression and activation of AMPK in adipose tissue of mice. In the present study, RPS increased the expression of p-AMPK/AMPK ratio compared with HFD-C group, in a dose-dependent manner (Fig. 3C, p = 0.028). These data suggest that RPS might be an activator of AMPK to suppress obesity in HFD-fed mice.

RPS improved insulin sensitivity and hyperlipidemia in HFD-fed mice

It has been well established that in the case of excess adipose tissue or obesity, particularly the visceral compartment, normal adipose tissue becomes enlarged, contributing to pro-inflammatory states, insulin resistance, hyperglycemia and hypertension (Guiherme et al., 2008; Kershaw and Flier, 2004; Sun et al., 2016).

To determine whether RPS affects insulin sensitivity, FBG and serum insulin levels were measured. HFD-C group significantly increased d FBG, insulin level, and HOMA-IR score compared with ND-C group. However, RPS groups improved insulin sensitivity as indicated by significantly reduced FBG, serum insulin, and HOMA-IR (Fig. 4A, p = 0.01). In common with serum lipids, these findings are in contrast to the results when HFD-fed mice were treated with 94% ethanol extract of defatted pepper seed or pepper seed extracted capsicoside G-rich fraction. The fasting blood glucose was not affected by supplement of ethanol extract of defatted pepper seed or capsicoside G-rich fraction (Sung et al., 2016a; 2016b). AMPK is identified as a novel regulatory pathway for insulin-like growth factor-binding protein 1 (IGFBP1) which is implicated in the mediation of insulin sensitivity (Lewitt, 2013; Minokoshi et al., 2002). Moreover, the activation of AMPK and the inhibition of ACC are believed to be partly linked to the metabolic effect of leptin, the deficiency of which is a known factor leading to severe insulin resistance (Minokoshi et al., 2002).

Fig. 4.

Fig. 4

Open in a new tab

Effects of RPS on the insulin sensitivity in C57BL/6 mice fed high fat diet. (A) HOMA-IR and (B) Serum lipids. Means with the same letter represent values that are not significantly different based on one-way ANOVA followed by Duncan’s multiple range test (p < 0.05). ND: normal diet + distilled water, HFD: 60% high fat diet + distilled water, HFD + RPS 100: 60% high fat diet + red pepper seed extract 100 mg/kg, HFD + RPS 200: 60% high fat diet + red pepper seed extract 200 mg/kg

Abdominal obesity induces adipose and hepatic inflammation, thereby inducing insulin resistance and leading to hypertriglyceridemia and hypercholesterolemia, which are important biomarkers of CVD (Austin et al., 1998; Miller et al., 2011; Taverne et al., 2013). In the present study, RPS-treated mice showed a decrease in TG and TC levels compared with HFD-C group (p = 0.021, p = 0.032, respectively) (Fig. 4B). Importantly, though no statistical significance was found, LDL-C level in the RPS supplementation groups were lower than that of the HFD-C group. These findings are also in contrast to the results when HFD-fed mice were treated with 94% ethanol extract of defatted pepper seed (Sung et al., 2016b) or pepper seed extracted capsicoside G-rich fraction (Sung et al., 2016a). The supplement of ethanol extract of defatted pepper seed or capsicoside G-rich fraction did not affect TG and TC levels (Sung et al., 2016a; 2016b).

The primary focus of obesity treatment is to decrease the risk of obesity-related diseases including CVD. Therefore, RPS is a promising agent for obesity treatment in the sense that anti-obesity agents can improve insulin resistance and dyslipidemia, thereby reducing the prevalence of obesity-related diseases. Moreover, it would be difficult to ascertain whether the anti-obesity effect of our RPS is associated with capsicoside G, owing to different effects observed on serum lipids and insulin sensitivity, and the variations in processing the pepper seed. More studies are therefore needed to elucidate which component of our RPS inhibits obesity.

Taken together, the findings suggest that RPS may have anti-obesity activity in vivo, offering a potentially promising new approach for the treatment of obesity and obesity-related diseases.

Acknowledgements

This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (115015-03-2-HD020).

Funding

Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET), Ministry of Agriculture, Food and Rural Affairs (MAFRA), Grant Number: 115015-03-2-HD020.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Hwa-Jin Kim, Email: tailove2212@naver.com.

Mi-Kyoung You, Email: budi1030@naver.cm.

Ziyun Wang, Email: wangziyun007@hotmail.com.

Young-Hyeon Lee, Email: ciesl7@naver.com.

Hyeon-A Kim, Email: kha@mokpo.ac.kr.

References

  1. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am. J. Cardiol. 1998;81:7–12. doi: 10.1016/S0002-9149(98)00031-9. [DOI] [PubMed] [Google Scholar]
  2. Barzilai N, Gupta G. Revisiting the role of fat mass in the life extension induced by caloric restriction. J. Gerontol. Series A, Biological Sciences and Medical Sciences 54: 89-96 (1999) [DOI] [PubMed]
  3. Choi WH, Um MY, Ahn J, Jung CH, Park MK, Ha TY. Ethanolic extract of Taheebo attenuates increase in body weight and fatty liver in mice fed a high-fat diet. Molecul. 2014;19:16013–16023. doi: 10.3390/molecules191016013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guiherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nature reviews. Mol. Cell Biol. 2008;9:367–377. doi: 10.1038/nrm2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ. The biology of white adipocyte proliferation. Obesity Rev. 2001;2:239–254. doi: 10.1046/j.1467-789X.2001.00042.x. [DOI] [PubMed] [Google Scholar]
  6. He Y, Li Y, Zhao T, Wang Y, Sun C. Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway. PLoS ONE. 2013;8(7):e70135. doi: 10.1371/journal.pone.0070135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hsu CL, Yen GC. Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. J. Agricul. Food Chem. 2007;55:1730–1736. doi: 10.1021/jf062912b. [DOI] [PubMed] [Google Scholar]
  8. Huang TT, Johnson MS, Goran MI. Development of a prediction equation for insulin sensitivity from anthropometry and fasting insulin in prepubertal and early pubertal children. Diabetes Care. 2002;25:1203–1210. doi: 10.2337/diacare.25.7.1203. [DOI] [PubMed] [Google Scholar]
  9. Iorizzi M, Lanzotti V, Ranalli G, De Marino S, Zollo F. Antimicrobial furostanol saponins from the seeds of Capsicum annuum L. var. acuminatum. J. Agric. Food Chem. 50: 4310-4316 (2002) [DOI] [PubMed]
  10. Jia S, Gao Z, Yan S, Chen Y, Sun C, Li X, Chen K. Anti-obesity and hypoglycemic effects of Poncirus trifoliata L. extracts in high-fat diet C57BL/6 mice. Molecules 21: 453 (2016) [DOI] [PMC free article] [PubMed]
  11. Kershaw EE, Flie JS. Adipose tissue as an endocrine organ. J. Clin. Endocri. Meta. 2004;89:2548–2556. doi: 10.1210/jc.2004-0395. [DOI] [PubMed] [Google Scholar]
  12. Ki HS, Han YS. The antimutagenic and antioxidant effects of red pepper seed and red pepper pericarp (Capsicum annuum L.). Preventive Nutri. Food Sci. 12: 273-278 (2007)
  13. Ki HS, Han YS. Antioxidant activities of red pepper (Capsicum annuum) pericarp and seed extracts. Int. J. Food Sci. Technol. 2008;43:1813–1823. doi: 10.1111/j.1365-2621.2008.01715.x. [DOI] [Google Scholar]
  14. Kim HJ, You MK, Wang Z, Kim HA. Red pepper seed inhibits differentiation of 3T3-L1 cells during the early phase of adipogenesis via the activation AMPK. Amer. J. Chinese med. 2018;46:107–118. doi: 10.1142/S0192415X18500064. [DOI] [PubMed] [Google Scholar]
  15. Lai CS, Ho MH, Tsai ML, Li S, Badmaev V, Ho CT, Pan MH. Suppression of adipogenesis and obesity in high-fat induced mouse model by hydroxylated polymethoxyflavones. J. Agricul. Food Chem. 2013;61:10320–10328. doi: 10.1021/jf402257t. [DOI] [PubMed] [Google Scholar]
  16. Lane MD, Tang QQ, Jiang MS. Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem. Biophys. Res. Commun. 1999;266:677–683. doi: 10.1006/bbrc.1999.1885. [DOI] [PubMed] [Google Scholar]
  17. Lee MS, Kim CT, Kim IH, Kim Y. Effects of capsaicin on lipid catabolism in 3T3-L1 adipocytes. Phytother. Res. 2011;25:935–939. doi: 10.1002/ptr.3339. [DOI] [PubMed] [Google Scholar]
  18. Lewitt MS. Effect of ghrelin on hepatic IGF-binding protein-1 production. ISRN Obesity 751401 (2013) [DOI] [PMC free article] [PubMed]
  19. Li KK, Liu CL, Shiu HT, Wong HL, Siu WS, Zhang C, Han XQ, Ye CX, Leung PC, Ko CH. Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes. Sci. Rep. 2016;6:20172. doi: 10.1038/srep20172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S. Triglycerides and cardiovascular disease: a scientific statement from the american heart association. Circulation 123: 2292-2333 (2011) [DOI] [PubMed]
  21. Minokoshi Y, Kim YB, Peroni OD, Fryer LGD, Müller C, Carling D, Kahn BB. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415: 339-343 (2002) [DOI] [PubMed]
  22. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156:20–44. doi: 10.1016/j.cell.2013.12.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sim KH, Han YS. The Antimutagenic and Antioxidant effects of red pepper seed and red pepper pericarp (Capsicum annuum L.). Korean Soc. Food Sci. Nutri. 12: 273-278 (2007)
  24. Song WY, Ku KH, Choi JH. Effect of ethanol extracts from red pepper seeds on antioxidative defense system and oxidative stress in rats fed high-fat high-cholesterol diet. Nutri. Res. Prac. 2010;4:11–15. doi: 10.4162/nrp.2010.4.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sun J, Ren F, Xiong L, Zhao L, Cuo H. Bovine lactoferrin suppresses high-fat diet induced obesity and modulates gut microbiota in C57BL/6 J mice. J. Funt. Foods. 2016;22:189–200. doi: 10.1016/j.jff.2016.01.022. [DOI] [Google Scholar]
  26. Sung JH, Jeong HS, Lee JS. Effect of the capsicoside G-rich fraction from pepper (Capsicum annuum L.) seeds on high-fat diet-induced obesity in mice. Phytother. Res. 30: 1848-1855 (2016a) [DOI] [PubMed]
  27. Sung JH, Yang JW, Kim YH, Kim MH, Jeong HS, Lee JS. Effect of defatted pepper (Capsicum annuum L.) seed extracts on high-fat diet-induced obesity in C57BL/6J mice. Food Sci. Biotechnol. 25: 1457-1461 (2016b) [DOI] [PMC free article] [PubMed]
  28. Taverne F, Richard C, Couture P, Lamarche B. Abdominal obesity, insulin resistance, metabolic syndrome and cholesterol homeostasis. Phar. Nutri. 2013;1:130–136. [Google Scholar]
  29. Wes DB, Boozer CN, Moody DL, Atkinson RL. Dietary obesity in nine inbred mouse strains. Ameri. J. Physiol. 1992;262:1025–1032. doi: 10.1152/ajpregu.1992.262.6.R1025. [DOI] [PubMed] [Google Scholar]
  30. Youn SH, Yin J, Ahn HS, Tam LT, Kwon SH, Min BK, Yun SH, Kim HY, Lee MW. Quantitativ analysis of icariside E5 and Vanilloyl icariside E5 from the seed of capsicum annuum. L. Kor. J. Phamaco. 2017;48:160–165. [Google Scholar]

Articles from Food Science and Biotechnology are provided here courtesy of Springer

RESOURCES