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Theobromine rich cocoa powder induces weight loss and changes in lipid profile of obese Wistar rats

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Abstract

Obesity (overweight) has remained a public health problem, on account of its attendant complications viz diabetes, hypertension and atherosclerosis. To arrest the significant decrease in life expectancy affiliated upon the older age group by obesity, dietary induced weight loss has been sought. This study assessed the effect of dietary theobromine (theobromine rich cocoa powder diets) on weight changes and lipid profile of Wistar rats. The inclusion of 3% to 15% cocoa powder in the diet corresponding to an estimated 56 +/- 15.15 to 265 +/- 0.13mg of theobromine intake for 28 days, induced a significant (P < 0.05) rapid weight loss in the rats exposed to the test diet relative to the controls, the weight loss becoming significant after about a week of exposure. Lipid profile analysis on day 28(th) showed a significant (P < 0.05) decrease in total serum cholesterol, triglycerides and VLDL cholesterol but HDL cholesterol was significantly (P < 0.05) elevated in treatments relative to controls. The biochemical role of theobromine in the observed weight loss is discussed in respect to lipid metabolism and dietary control of obesity.

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... The alleviating effect of TB on weight gain through its modifying effect on the gut microbiota in rodents, has also been reported (Martín-Peláez et al., 2017). It has also been shown that a TB-rich diet could attenuate body weight gain in rats (Eteng et al., 2006). Furthermore, the improving effects of TB on serum lipoprotein profiles, inflammatory factors, and vascular function have been reported in several studies (Baggott et al., 2013;Bhat et al., 2021;Bhat & Kumar, 2022;Mitchell et al., 2011;Neufingerl et al., 2013;Smolders et al., 2018). ...
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Theobromine may have beneficial effects on cardiovascular risk factors. This study aimed to find molecular effects of theobromine on lipid profile, glycemic status, inflammatory factors, and vascular function through a comprehensive assessment of all in vitro and in vivo studies. The search process was started at 18 July 2022. Databases including PubMed, Scopus, and Web of Science were searched to find all articles published up to 18 July 2022. Nineteen studies were included in this study. In vitro studies showed the improving effects of theobromine on inflammatory markers. Of four animal studies assessing the effect of theobromine on inflammatory markers, two reported favorable effects. Among five animal studies assessing the effects of theobromine on lipid profile, three reported improving effects on either triglyceride, total cholesterol, low- or high-density lipoprotein cholesterol. Of the three human studies, two revealed that theobromine had improving effects on lipid profile. A favorable effect of theobromine on augmentation index was also reported in two RCTs. The results for other outcomes were inconclusive. Theobromine may have favorable effects on inflammatory factors, lipid profile, and vascular function markers. However, studies with a longer duration and lower, dietary-relevant doses are required for future confirmation.
... Theobromine among other methylxanthines has a very low in uence on the central nervous system, probably due to poor physicochemical properties necessary for distribution in that system (Beale Jr 2011). Results of Eteng et al. showed that theobromine-rich cocoa powder induces weight loss and changes in the lipid pro le of obese rats (Eteng et al. 2006). Other results suggested that theobromine inhibits adipocyte differentiation during the early stages of adipogenesis (Jang et al. 2015). ...
Chapter
This chapter covers methylxanthines, with a focus on caffeine, theophylline, and theobromine. The key topics of the chapter cover the chemical structure of methylxanthines, their potential in nutrition, and a broad spectrum of biological functions for pharmacological applications. The content of methylxanthines in food and their bioavailability are also discussed, as well as growing applications in functional food products and dietary supplements. The final section covers briefly the current analytical methodologies and techniques applied in the analysis of methylxanthines.
... In addition, theobromine improves blood lipoprotein profiles, thereby mitigating cardioprotective effects in humans [16], and has a capability of modifying the gut microbiota in rodents, thereby alleviating weight gain in rats [15]. Furthermore, it has been shown that a diet with theobromine-rich powder alleviated body weight gain in rats [17]. ...
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Purpose Modern science has given much attention to the treatment of obesity by activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Recent studies have identified theobromine, a derivative of cocoa, as a potent natural component actively browning white fat cells. Here, we aimed to deduce the anti-obesity effect of theobromine involving phosphodiesterase (PDE) dependent-regulatory pathway in obese animal models. Methods For examining activity of theobromine, C57BL/6 mice were fed with high fat diet and treated with theobromine to determine the expression levels of protein markers by immunoblot analysis and gene targets by quantitative real-time PCR. Other methods used include histopathological studies, immunofluorescence and molecular docking approaches. Results Theobromine alleviated diet-induced obesity in mice by browning of iWAT and activating BAT. Further, theobromine actively interacted with PDE4D and inhibited its activity in adipose tissues and cells potentiating energy expenditure. Moreover, the regulatory action of theobromine via inhibition of PDE4D was mediated by β3-AR signaling pathway. Conclusion Altogether, the current results signifies critical role of theobromine in reducing obesity by regulation of lipid metabolism through inhibition of PDE4, indicating its potential as a major therapeutic medicinal compound.
... Recent meta-analyses suggest that consumption of dietary flavanol-containing substances could reduce body mass index (BMI) and waist circumference (WC) (Gonz alez-Sarr ıas et al., 2017).Cocoa specifically contains a large amount of epicatechin, catechin and procyanidins (Miller et al., 2009, Habauzit and Morand, 2012, Manach et al., 2004, Neveu et al., 2010. Although the exact mechanisms were not clarified yet, following probable pathways have been suggested: 1) Improving insulin sensitivity and weight loss because of cocoa-derived active components (Bowser et al., 2017, Dorenkott et al., 2014, Eteng et al., 2006, Lazaro, Luz, and Sapang 2014. 2) Decrease the expression of genes involved in the biosynthesis of fatty acids, cholesterol and lipogenesis (Latif, 2013, Matsui et al., 2005. ...
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ABSTRACT Background: Cocoa and dark chocolate (DC) have been reported to be effective for health promotion; however the exact effect of cocoa/DC on anthropometric measures have not been yet defined. Methods: A comprehensive search to identify randomized clinical trials investigating the impact of cocoa/ DC on body weight, body mass index (BMI) and waist circumference (WC) was performed up to December 2017. A meta-analysis of eligible studies was performed using random effects model to estimate pooled effect size. Fractional polynominal modeling was used to explore dose-response relationships. Results: A total of 35 RCTs investigated the effects of cocoa/DC on weight, BMI and WC were included. Meta-analysis did not suggest any significant effect of cocoa/DC supplementation on body weight (¡0.108 kg, 95% CI ¡0.262, 0.046 P D 0.168), BMI (¡0.014 kg/m2 95% CI ¡0.105, 0.077, P: 0.759,) and WC (0.025 cm 95% CI ¡0.083, 0.129, P D 0.640). Subgroup analysis revealed that that weight and BMI were reduced with cocoa/DC supplementation � 30 g chocolate per day in trials between 4-8 weeks. Cocoa/DC consumption resulted in WC reduction in non-linear fashion (r D 0.042, P-nonlinearity D 0.008). Conclusion: Cocoa/DC supplementation does not reduce anthropometric measures significantly. However subgroup analysis regarding dose (� 30 g/day) and duration (between 4 to 8 weeks) revealed significant reduction of body weight and BMI.
... An earlier report demonstrated that cocoa tea supplementation improves high-fat diet-induced obesity and hyperlipidemia in mice [15] and has the capacity to suppress adipogenesis in 3T3-L1 preadipocytes, similar to traditional green tea [16]. Furthermore, it has been shown that a diet with theobromine-rich powder promoted weight loss in rats [17]. ...
Article
Natural medicinal compounds to treat obesity have recently attracted a great deal of attention because of the serious side effects of synthetic anti-obesity drugs. Recent advances have been made to identify natural products showing thermogenic activity, which is responsible for energy expenditure in brown or brown-like (beige) adipocytes. Here, we explored the thermogenic effects of theobromine, one of the most abundant methylxanthines in cocoa, on 3T3-L1 white adipocytes and HIB1B brown adipocytes. Theobromine markedly increased the expression levels of brown-fat signature proteins (PGC-1α, PRDM16, and UCP1) and beige-specific genes (Cd137, Cidea, Cited1, Tbx1, and Tmen26) in 3T3-L1 white adipocytes and remarkably elevated the expression levels of brown fatspecific genes (Cidea, Lhx8, Ppargc1, Prdm16, Ucp1, and Zic1) in HIB1B brown adipocytes. Theobromine also reduced the expression of the key adipogenic transcription factors, C/EBPα and PPARγ, in white adipocytes, while enhancing their expression in HIB1B cells. In addition, theobromine regulated lipolytic events and fat oxidation by upregulating the expression of pACC, ATGL, pHSL, ACOX, and CPT1. Additional mechanistic study revealed that theobromine activates β3-AR and AMPK. In summary, our results provide evidence for the first time indicating that theobromine has a potential beneficial effect on browning of white adipocytes and improves lipid catabolic metabolism in both cultured white and brown adipocytes via β-adrenergic signaling and AMPK activation. Consumption of theobromine may be a feasible way to activate thermogenesis and improve systematic lipid metabolism to protect against obesity and other metabolic disorders.
... Recent meta-analyses suggest that consumption of dietary flavanol-containing substances could reduce body mass index (BMI) and waist circumference (WC) (Gonz alez-Sarr ıas et al., 2017).Cocoa specifically contains a large amount of epicatechin, catechin and procyanidins (Miller et al., 2009, Habauzit and Morand, 2012, Manach et al., 2004, Neveu et al., 2010. Although the exact mechanisms were not clarified yet, following probable pathways have been suggested: 1) Improving insulin sensitivity and weight loss because of cocoa-derived active components (Bowser et al., 2017, Dorenkott et al., 2014, Eteng et al., 2006, Lazaro, Luz, and Sapang 2014. 2) Decrease the expression of genes involved in the biosynthesis of fatty acids, cholesterol and lipogenesis (Latif, 2013, Matsui et al., 2005. ...
Article
Full-text available
Background Cocoa and dark chocolate (DC) have been reported to be effective for health promotion; however the exact effect of cocoa/DC on anthropometric measures have not been yet defined. Methods A comprehensive search to identify randomized clinical trials(RCT)s investigating the impact of cocoa/DC on body weight, body mass index (BMI) and waist circumference(WC) was performed up to December 2017. A meta-analysis of eligible studies was performed using random effects model to estimate pooled effect size. Fractional polynominal modeling was used to explore dose-response relationships for cocoa/DC supplementation. Results A total of 35 RCTs investigated the effects of cocoa/DC on weight, BMI and WC were included. Meta-analysis did not suggest any significant effect of cocoa/DC supplementation on body weight (-0.108 kg,95% CI -0.262, 0.046 P = 0.168), BMI (-0.014 kg/m²95% CI -0.105, 0.077, P: 0.759,) and WC (0.025 cm95% CI -0.083, 0.129, P = 0.640). Subgroup analysis revealed that that weight and BMI were reduced with cocoa/DC supplementation ≥30g chocolate per day in trials between 4–8 weeks. Chocolate consumption resulted in WC reduction in non-linear fashion (r = 0.042, P-nonlinearity = 0.008). Conclusion Cocoa/DC supplementation reduced body weight, BMI and WC. Dose and duration were important determinates for favorable effects on anthropometric measures.
... The combination of 0.05% caffeine and 0.3% green tea's catechins was the most effective for preventing weight gain, in comparison with the normal diet group from the 4th to the 16th week. Furthermore, it was also shown that a diet with a theobrominerich cocoa powder promoted weight loss in Wistar rats, compared to control (Eteng et al., 2006). ...
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... Some phytochemicals more abundant in AI than VA leaves including tannins, alkaloids and hydrocyanic acids reported ealier (Atangwho et al., 2009) may have endowed it this selective action over VA. Tannins have been implicated in hypolipidemic effects (Nimenibo-Uadia, 2003) and alkaloids from cocoa were also reported to ameliorate dietarily induced obesity in rats via their hypolipidemic action (Eteng et al., 2006). However when administered in combination, this solo effect of AI extract was effectively modulated by VA extract and the indices brought to levels similar to normal control. ...
... However, no effect on lipid profiles was observed after administration of cocoa extract, compared to pure theobromine. Eteng et al. [103] reported that supplementations of 3% and 15% cocoa powder that contained 56 to 265 mg theobromine to the rats significantly reduced body weight and also decreased lipid profiles. These results indicated that cocoa possessed hypocholesterolemic properties, in contrast to the first study. ...
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In 1737, the cocoa tree was named Theobroma cacao L. which refers to the mythicalbackground of the tree literally means "cocoa, food of the gods". Cocoa and their relatedproducts derived from this tree had been used by our ancestors to treat various types ofailments. In the 17th and 18th century, cocoa was regularly prescribed or mixed intomedications for all sorts of ailments and diseases from colds and coughing, to promotedigestion, fertility, reinforce mental performance and as an anti-depressant. The empiricalfindings of cocoa and cocoa-derived products on health benefits were uncovered only inthe 21st century owing to their exemplary amount of dietary antioxidants (flavonoids).Scrumptious taste and their roles in combating risk factors for chronic diseases are thetwo main reasons that staggered most of the modern scientists. Up-to-date there were vastarray of scientific evidence published on the contribution of cocoa and cocoa-derivedproducts towards health. Studies originated from in vitro, in vivo and human clinical trialsstrongly supported that polyphenols especially flavonoids present in cocoa and theirproducts were absorbable and made bioavailable in the digestive system; and exertedmultiple health benefits in reducing disease risk factors, preventing disease progression and ameliorating disease severity. This chapter is then delineated an insight of cocoapolyphenols' chemistry and their putative effects on our health.
... Some phytochemicals more abundant in AI than VA leaves including tannins, alkaloids and hydrocyanic acids reported ealier (Atangwho et al., 2009) may have endowed it this selective action over VA. Tannins have been implicated in hypolipidemic effects (Nimenibo-Uadia, 2003) and alkaloids from cocoa were also reported to ameliorate dietarily induced obesity in rats via their hypolipidemic action (Eteng et al., 2006). However when administered in combination, this solo effect of AI extract was effectively modulated by VA extract and the indices brought to levels similar to normal control. ...
... However, no effect on lipid profiles was observed after administration of cocoa extract, compared to pure theobromine. Eteng et al. [103] reported that supplementations of 3% and 15% cocoa powder that contained 56 to 265 mg theobromine to the rats significantly reduced body weight and also decreased lipid profiles. These results indicated that cocoa possessed hypocholesterolemic properties, in contrast to the first study. ...
Article
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Cocoa and cocoa products have received much attention due to their significant polyphenol contents. Cocoa and cocoa products, namely cocoa liquor, cocoa powder and chocolates (milk and dark chocolates) may present varied polyphenol contents and possess different levels of antioxidant potentials. For the past ten years, at least 28 human studies have been conducted utilizing one of these cocoa products. However, questions arise on which of these products would deliver the best polyphenol contents and antioxidant effects. Moreover, the presence of methylxanthines, peptides, and minerals could synergistically enhance or reduce antioxidant properties of cocoa and cocoa products. To a greater extent, cocoa beans from different countries of origins and the methods of preparation (primary and secondary) could also partially influence the antioxidant polyphenols of cocoa products. Hence, comprehensive studies on the aforementioned factors could provide the understanding of health-promoting activities of cocoa or cocoa products components.
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Dysregulation of glucose metabolism is a primary hallmark of metabolic disease (i.e. diabetes, obesity, etc.). Complementary non-pharmaceutical strategies are needed to prevent and/or ameliorate dysregulation of glucose metabolism and prevent progression from normoglycemia to prediabetes and type-2 diabetes across the lifespan. Cocoa compounds, particularly the procyanidins, have shown promise for improving insulin sensitivity and blood glucose homeostasis. However, the molecular mechanisms by which cocoa procyanidins exert these functions remain poorly understood. Furthermore, cocoa procyanidins exhibit size diversity, and evidence suggests that procyanidin bioactivity and size may be related. Here, we show that a procyanidin-rich cocoa extract elicits an anti-diabetic effect by stimulating glycogen synthesis and glucose uptake, independent of insulin. Cocoa procyanidins did not appear to act via stimulation of AMPK or CaMKII activities. Additionally, in the presence of insulin, glycogen synthesis and AKT phosphorylation were affected. These mechanisms of action are most pronounced in response to oligomeric and polymeric procyanidins. These results demonstrate 1) specific mechanisms by which cocoa procyanidins improve glucose utilization in skeletal muscle and 2) that larger procyanidins appear to possess enhanced activities. These mechanistic insights suggest specific strategies and biological contexts that may be exploited to maximize the anti-diabetic benefits of cocoa procyanidins.
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There is interest in the potential of cocoa flavanols, including monomers and procyanidins, to prevent obesity and type-2 diabetes. Fermentation and processing of cocoa beans influence the qualitative and quantitative profiles of individual cocoa constituents. Little is known regarding how different cocoa flavanols contribute to inhibition of obesity and type-2 diabetes. The objective of this study was to compare the impacts of long-term dietary exposure to cocoa flavanol monomers, oligomers and polymers on the effects of high-fat feeding. Mice were fed a high-fat diet supplemented with either a cocoa flavanol extract, or a flavanol fraction enriched with monomeric, oligomeric, or polymeric procyanidins for 12 weeks. The oligomer-rich fraction proved to be most effective in preventing weight gain, fat mass, impaired glucose tolerance, and insulin resistance in this model. This is the first long-term feeding study to examine the relative activities of cocoa constituents on diet-induced obesity and insulin resistance.
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Caffeine and theobromine are purine alkaloids widely consumed as stimulants and snacks in coffee and cocoa based foods and most often as part of ingredients in drugs. Man has enjoyed a long history of consumption of caffeine and theobromine. Recent interest in these two alkaloids, however, is centered on their potential reproductive toxicities. Caffeine and theobromine are now known to cross the placental and blood brain barrier thus potentially inducing fetal malformation by affecting the expression of genes vital in development. The developing fetus may not have developed enzymes for detoxification of these methylxanthine alkaloids via demethylation. There is a need, therefore, to protect the conceptus against 'insults' from teratogens of this nature. Apart from its reproductive toxicity, the presence of caffeine and theobromine in cocoa could limit its potentials as a nourishing food. This is an issue that needs to be addressed by nutritionists and the food industry at large. This paper discusses the natural sources, consumption and uses, toxicity and the major advances in the reproductive toxicology of caffeine and theobromine. The biosynthesis of these compounds in plants, metabolism in mammalian systems and the involvement of cytochrome P450 are reviewed and summarized. Evidence in favor of the toxicity of these compounds in experimental animals is presented with emphasis on the implications of these findings in humans. The paper concludes with a call for caution in the use of caffeine and theobromine pending further and more elaborate investigations.