The Structure Basis of Phytochemicals as Metabolic Signals for Combating Obesity

Abstract

The consumption of phytochemicals, bioactive compounds in fruits and vegetables, has been demonstrated to ameliorate obesity and related metabolic symptoms by regulating specific metabolic pathways. This review summarizes the progress made in our understanding of the potential of phytochemicals as metabolic signals: we discuss herein selected molecular mechanisms which are involved in the occurrence of obesity that may be regulated by phytochemicals. The focus of our review highlights the regulation of transcription factors toll like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the peroxisome proliferator-activated receptors (PPARs), fat mass and obesity-associated protein (FTO) and regulation of microRNAs (miRNA). In this review, the effect of phytochemicals on signaling pathways involved in obesity were discussed on the basis of their chemical structure, suggesting molecular mechanisms for how phytochemicals may impact these signaling pathways. For example, compounds with an isothiocyanate group or an α, β-unsaturated carbonyl group may interact with the TLR4 signaling pathway. Regarding Nrf2, we examine compounds possessing an α, β-unsaturated carbonyl group which binds covalently with the cysteine thiols of Keap1. Additionally, phytochemical activation of PPARs, FTO and miRNAs were summarized. This information may be of value to better understand how specific phytochemicals interact with specific signaling pathways and help guide the development of new drugs to combat obesity and related metabolic diseases.

Association of Plant-Based and High-Protein Diets with a Lower Obesity Risk Defined by Fat Mass in Middle-Aged and Elderly Persons with a High Genetic Risk of Obesity

“…There are various hypotheses about how a plant-based diet may help maintain a healthy body weight. First, a plant-based diet has a lower energy density, resulting in greater satiety and lower energy consumption [ 22 , 36 ]. Furthermore, plant-based diets contain lower fat and higher fiber, which may impact the microbiome, which is known to have substantive impacts on energy utilization in humans [ 37 , 38 , 39 ].…”

“…Models 1 and 2 indicated the results with different covariates. Ten-fold cross-validation was also checked for cross-validation consistency (CVC) because the sample size was larger than 1000 [ 22 ]. In total, 10 out of 10 in the CVC met the perfect cross-validation criteria.…”

Plant-based and high protein diets are associated with a lower risk of obesity among Koreans at a high genetic risk of obesity.

“…Descriptive statistics of the continuous variables were analyzed as the adjusted means with standard deviations after adjusting for the covariates. The statistical differences among the gender and insulin resistance groups were compared using a two-way analysis of covariance (ANCOVA) [19]. Multiple comparisons of the groups were performed using a Tukey's test.…”

“…However, the microbiome research has not progressed to the point that changes in the gut microbiome can be considered a cause or cure for excess body weight. There is also evidence that various phytochemicals from plant-based foods and dietary supplements may have antiobesity effects by various mechanisms [19]. It has been shown that the anti-in ammatory properties of plant-based diets can prevent obesity and even result in a healthier obese phenotype in people who become obese [36].…”

A New Frontier in Studying Dietary Phytochemicals in Cancer and in Health: Metabolic and Epigenetic Reprogramming

“…Biologically active phytochemicals are compounds with diverse chemical structures found in plants that exert many health beneficial biological effects and possess diverse molecular mechanisms including epigenetics ( Table 1 ) ( Fang et al, 2003 ; Chen et al, 2004 ; Fang et al, 2005 ; Druesne-Pecollo et al, 2007 ; Choi et al, 2009 ; Ho et al, 2009 ; Balasubramanian et al, 2010 ; Wu et al, 2011 ; Gong et al, 2012 ; An et al, 2013 ; Kang et al, 2013 ; Wang et al, 2014 ; Guo et al, 2015 ; Jiang et al, 2016 ; Kala and Tollefsbol, 2016 ; Li et al, 2017b ; Gao and Tollefsbol, 2018 ; Cremonini et al, 2019 ; Kuo et al, 2019 ; Yang et al, 2019 ; Wu et al, 2020 ). For a long time, they have been used for the protection and treatment of various diseases, such as diabetic nephropathy ( Hudlikar et al, 2021 ), obesity ( Martin et al, 2013 ; Dincer and Yuksel, 2021 ; Li et al, 2022c ), and cancer ( Lee et al, 2011 ; Kotecha et al, 2016 ). In general, mounting evidence shows that dietary phytochemicals are potent chemopreventive/cancer interceptive agents due to their antioxidant, metabolic modulation, and epigenetic regulation properties ( Gerhauser, 2013 ; Thakur et al, 2014 ; Russo et al, 2017 ; Wu et al, 2022 ).…”