Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet

Zhou, Jihong; Mao, Limin; Xu, Ping; Wang, Yuefei

doi:10.3390/nu10111681

Cited by 67 publications

(72 citation statements)

References 51 publications

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“…Among the polyphenols found in goat's milk, gallic acid, chlorogenic acid, ferulic acid and catechins are the most abundant [10], which have demonstrated to have antioxidant properties [32][33][34], increase in energy expenditure in mice [35] and humans [36] and anti-inflammatory properties [37]. Thus, the polyphenol content in goat's milk could be directly responsible of the increase in energy expenditure.…”

Section: Discussionmentioning

confidence: 99%

Goat’s Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle

Delgadillo-Puga

Noriega

Morales-Romero

et al. 2020

IJMS

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Goat’s milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat’s milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat’s milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat’s milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.

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Section: Discussionmentioning

confidence: 99%

Goat’s Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle

Delgadillo-Puga

Noriega

Morales-Romero

et al. 2020

IJMS

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“…In a subsequent study using HFD-induced obese C57BL/6J mice to investigate how EGCG regulates the thermogenic activity of BAT and hypothalamic inflammation, it was found that the development of diet-induced obesity was prevented upon 4 week dietary EGCG supplementation (100). In particular, experimental findings revealed an increase in the mRNA expression of BAT mitochondrial biogenesis and thermogenesis genes (Ucp1, Pgc-1α, and Prdm16), a rise in body temperature upon cold exposure, as well as a decrease in body weight gain, blood glucose and total triglyceride levels, adipose tissue lipid accumulation and microglia-mediated inflammation in the hypothalamus (via the inhibition of NF-κB and STAT3 pathways) (100). Together, these results show that EGCG led to an enhancement of BAT thermogenesis and amelioration of neuroinflammation in obese mice.…”

Section: Epigallocatechin-3-gallatementioning

confidence: 99%

Regulation of Thermogenic Adipocyte Differentiation and Adaptive Thermogenesis Through Histone Acetylation

et al. 2020

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Over the past decade, the increasing prevalence of obesity and its associated metabolic disorders constitutes one of the most concerning healthcare issues for countries worldwide. In an effort to curb the increased mortality and morbidity derived from the obesity epidemic, various therapeutic strategies have been developed by researchers. In the recent years, advances in the field of adipocyte biology have revealed that the thermogenic adipose tissue holds great potential in ameliorating metabolic disorders. Additionally, epigenetic research has shed light on the effects of histone acetylation on adipogenesis and thermogenesis, thereby establishing the essential roles which histone acetyltransferases (HATs) and histone deacetylases (HDACs) play in metabolism and systemic energy homeostasis. In regard to the therapeutic potential of thermogenic adipocytes for the treatment of metabolic diseases, herein, we describe the current state of knowledge of the regulation of thermogenic adipocyte differentiation and adaptive thermogenesis through histone acetylation. Furthermore, we highlight how different HATs and HDACs maintain the epigenetic transcriptional network to mediate the pathogenesis of various metabolic comorbidities. Finally, we provide insights into recent advances of the potential therapeutic applications and development of HAT and HDAC inhibitors to alleviate these pathological conditions.

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“…Evidence indicates that EGCG can prevent STAT3 activation by binding and interacting with the Arg-609 residue within the STAT3 SH2 domain, the domain responsible for STAT3 and peptide binding [ 88 ]. The inhibition of STAT3 by EGCG may be responsible for its antitumour and anti-adipogenic effect [ 88 , 117 , 118 , 119 , 120 ]. In hepatocellular carcinoma, the EGCG-mediated inhibition of STAT3 phosphorylation led to the reduction of downstream target genes encoding Bcl-xL, c-Myc, VEGF and Cyclin D1, resulting in the suppression of cell proliferation and the induction of apoptosis [ 88 ].…”

Section: Phytochemicalsmentioning

confidence: 99%

“…EGCG has been widely studied for its role as an anti-obesity agent, due to its ability to suppress adipocyte differentiation and proliferation [ 108 ]. EGCG demonstrated a suppressive action on lipid accumulation and pro-inflammatory cytokines in vitro and in vivo [ 120 , 122 , 123 ]. Palmitic acid (PA) has been shown to increase the invasiveness of several cancers via the induction of lipid accumulation and proinflammatory cytokine release [ 118 , 123 ].…”

Section: Phytochemicalsmentioning

confidence: 99%

“…The treatment of PA-stimulated microglia cells with EGCG prevented JAK2 and STAT3 phosphorylation, and attenuated lipid accumulation and inflammatory responses [ 123 ]. High-fat diet-fed mice receiving EGCG supplements showed a reduction in bodyweight, lipid deposition and adipocyte size, in addition to a decline in inflammatory cytokines such as TNFα, IL-6 and IL-1β, via the suppression of NF-κB [ 120 , 123 ]. EGCG can block adipocyte differentiation via reducing the expression of VEGF, C/EBPα and PPARγ [ 118 , 119 ].…”

Section: Phytochemicalsmentioning

confidence: 99%

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Phytochemical Targeting of STAT3 Orchestrated Lipid Metabolism in Therapy-Resistant Cancers

et al. 2020

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Lipids are critical for maintaining homeostasis and cellular metabolism. However, the dysregulation of lipid metabolism contributes to the pathogenesis of chronic inflammatory diseases and is a hallmark of several cancer types. Tumours exist in a microenvironment of poor vascularization-depleted oxygen and restricted nutrients. Under these conditions, tumours have been shown to increasingly depend on the metabolism of fatty acids for sustained proliferation and survival. Signal transducer and activator of transcription 3 (STAT3) plays a key role in cellular processes such as cell growth, apoptosis and lipid metabolism. Aberrant STAT3 activity, as seen in several cancer types, is associated with tumour progression and malignancy, in addition to propagating crosstalk between tumour cells and the microenvironment. Furthermore, STAT3-regulated lipid metabolism is critical for cancer stem cell self-renewal and therapy resistance. Plant-derived compounds known as phytochemicals are a potential source for novel cancer therapeutic drugs. Dietary phytochemicals are known to modulate key cellular signalling pathways involved in lipid homeostasis and metabolism, including the STAT3 signalling pathways. Targeting STAT3 orchestrated lipid metabolism has shown therapeutic promise in human cancer models. In this review, we summarize the antitumour activity of phytochemicals with an emphasis placed on their effect on STAT3-regulated lipid metabolism and their role in abrogating therapy resistance.

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Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet

Cited by 67 publications

References 51 publications

Goat’s Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle

Goat’s Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle

Regulation of Thermogenic Adipocyte Differentiation and Adaptive Thermogenesis Through Histone Acetylation

Phytochemical Targeting of STAT3 Orchestrated Lipid Metabolism in Therapy-Resistant Cancers

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