Breaking of integrability and conservation leading to Hamiltonian chaotic system and its energy-based coexistence analysis.

In this paper, a four-dimensional conservative system of Euler equations producing the periodic orbit is constructed and studied. The reason that a conservative system often produces periodic orbit has rarely been studied. By analyzing the Hamiltonian and Casimir functions, three invariants of the conservative system are found. The complete integrability is proved to be the mechanism that the system generates the periodic orbits. The mechanism route from periodic orbit to conservative chaos is found by breaking the conservation of Casimir energy and the integrability through which a chaotic Hamiltonian system is built. The observed chaos is not excited by saddle or center equilibria, so the system has hidden dynamics. It is found that the upgrade in the Hamiltonian energy level violates the order of dynamical behavior and transitions from a low or regular state to a high or an irregular state. From the energy bifurcation associated with different energy levels, rich coexisting orbits are discovered, i.e., the coexistence of chaotic orbits, quasi-periodic orbits, and chaotic quasi-periodic orbits. The coincidence between the two-dimensional diagram of maximum Lyapunov exponents and the bifurcation diagram of Hamiltonian energy is observed. Finally, field programmable gate array implementation, a challenging task for the chaotic Hamiltonian conservative system, is designed to be a Hamiltonian pseudo-random number generator.

Analysis of second outbreak of COVID-19 after relaxation of control measures in India.

At present, more and more countries have entered the parallel stage of fighting the epidemic and restoring the economy after reaching the inflection point. Due to economic pressure, the government of India had to implement a policy of relaxing control during the rising period of the epidemic. This paper proposes a compartment model to study the development of COVID-19 in India after relaxing control. The Sigmoid function reflecting the cumulative effect is used to characterize the model-based diagnosis rate, cure rate and mortality rate. Considering the influence of the lockdown on the model parameters, the data are fitted using the method of least squares before and after the lockdown. According to numerical simulation and model analysis, the impact of India's relaxation of control before and after the inflection point is studied. Research shows that adopting a relaxation policy prematurely will have disastrous consequences. Even if the degree of relaxation is only 5% before the inflection point, it will increase the number of deaths by 15.03%. If the control is relaxed after the inflection point, the higher degree of relaxation, the more likely a secondary outbreak will occur, which will extend the duration of the pandemic, leading to more deaths and put more pressure on the health care system. It is found that after the implementation of the relaxation policy, medical quarantine capability and public cooperation are two vital indicators. The results show that if the supply of kits and detection speed can be increased after the control is relaxed, the secondary outbreak can be effectively avoided. Meanwhile, the increase in public cooperation can significantly reduce the spread of the virus, suppress the second outbreak of the pandemic and reduce the death toll. It is of reference significance to the government's policy formulation.

Modeling and staged assessments of the controllability of spread for repeated outbreaks of COVID-19.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been causing an outbreak of a new type of pneumonia globally, and repeated outbreaks have already appeared. Among the studies on the spread of the COVID-19, few studies have investigated the repeated outbreaks in stages, and the quantitative condition of a controllable spread has not been revealed. In this paper, a brief compartmental model is developed. The effective reproduction number (ERN) of the model is interpreted by the ratio of net newly infectious individuals to net isolation infections to assess the controllability of the spread of COVID-19. It is found that the value of the ERN at the inflection point of the pandemic is equal to one. The effectiveness of the quarantine, even the treatment, is parametrized in various stages with Gompertz functions to increase modeling accuracy. The impacts of the vaccinations are discussed by adding a vaccinated compartment. The results show that the sufficient vaccinations can make the inflection point appear early and significantly reduce subsequent increases in newly confirmed cases. The analysis of the ERNs of COVID-19 in the United States, Spain, France, and Peru confirms that the condition of a repeated outbreak is to relax or lift the interventions related to isolation and quarantine interventions to a level where the ERN is greater than one.

Modeling and Analysis of a Three-Terminal-Memristor-Based Conservative Chaotic System.

In this paper, a three-terminal memristor is constructed and studied through changing dual-port output instead of one-port. A new conservative memristor-based chaotic system is built by embedding this three-terminal memristor into a newly proposed four-dimensional (4D) Euler equation. The generalized Hamiltonian energy function has been given, and it is composed of conservative and non-conservative parts of the Hamiltonian. The Hamiltonian of the Euler equation remains constant, while the three-terminal memristor's Hamiltonian is mutative, causing non-conservation in energy. Through proof, only centers or saddles equilibria exist, which meets the definition of the conservative system. A non-Hamiltonian conservative chaotic system is proposed. The Hamiltonian of the conservative part determines whether the system can produce chaos or not. The non-conservative part affects the dynamic of the system based on the conservative part. The chaotic and quasiperiodic orbits are generated when the system has different Hamiltonian levels. Lyapunov exponent (LE), Poincaré map, bifurcation and Hamiltonian diagrams are used to analyze the dynamical behavior of the non-Hamiltonian conservative chaotic system. The frequency and initial values of the system have an extensive variable range. Through the mechanism adjustment, instead of trial-and-error, the maximum LE of the system can even reach an incredible value of 963. An analog circuit is implemented to verify the existence of the non-Hamiltonian conservative chaotic system, which overcomes the challenge that a little bias will lead to the disappearance of conservative chaos.

Effects of control measures on the dynamics of COVID-19 and double-peak behavior in Spain.

The COVID-19 disease significantly has threatened the human lives and economy. It is a dynamic system with transmission and control as factors. Modeling the dynamics of the spread of COVID-19 based on the reported data can predict the growing trend of such a disease. In this paper, the dynamic evolution of COVID-19 in Spain is studied, and a comprehensive SEIR model is adopted to fit the obtained clinical progressive data of COVID-19 in Spain. The transmission rate between the susceptible and the self-quarantine susceptible is made to be time-variant, which is reasonable. The equilibria are found, and the stability condition is given using the basic reproduction number and eigenvalues at the points. The effect on daily confirmed cases for the transmission rate from susceptible to the exposed population due to the currently exposed and infectious is extensively investigated. The risk of the easing of the control measure is investigated. The double-peak dynamic behavior of the COVID-19 system is observed. The second wave rebound shows that the daily confirmed cases of the second peak even much higher than the first peak.

Nobiletin protects against insulin resistance and disorders of lipid metabolism by reprogramming of circadian clock in hepatocytes.

SCOPE: Circadian clock plays a principal role in orchestrating our daily physiology and metabolism, and their perturbation can evoke metabolic diseases such as fatty liver and insulin resistance. Nobiletin (NOB) has been demonstrated to possess antitumor and neuroprotective activities. The objective of the current study is to determine potential effects of NOB on modulating the core clock gene Bmal1 regarding ameliorating glucolipid metabolic disorders. RESULTS: Our results revealed that NOB partially reverse the relatively shallow daily oscillations of circadian clock genes and reset phase-shifting circadian rhythms in primary hepatocytes under metabolic disorders conditions. Importantly, NOB was found to be effective at amplifying glucose uptake via stimulating IRS-1/AKT signaling pathway, as well as blunting palmitate-induced lipogenesis in HepG2 cells via modulating AMPK-Sirt1 signaling pathway and key enzymes of de novo lipogenesis in a Bmal1-dependent manner. NOB attenuated palmitate-stimulated excessive secretions of ROS, restored the depletions of mitochondrial membrane potential, which is similar to the recovery in expressions of mitochondrial respiration complex I-IV. CONCLUSION: This study is the first to provide compelling evidences that NOB prevent cellular glucolipid metabolic imbalance and mitochondrial function in a Bmal1-dependent manner. Overall, NOB may serve as a nutritional preventive strategy in recovering metabolic disorders relevant to circadian clock.

EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.

Obesity, which is caused by an energy imbalance between calorie intake and consumption, has become a major international health burden. Obesity increases the risk of insulin resistance and age-related cognitive decline, accompanied by peripheral inflammation. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, possesses antioxidant, anti-inflammatory, and cardioprotective activities; however, few reports have focused on its potential effect on cognitive disorders. In this study, our goal was to investigate the protective effects of EGCG treatment on insulin resistance and memory impairment induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo-old C57BL/6J mice to 3 groups with different diets: control group, HFFD group, and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze test, during which EGCG was observed to prevent HFFD-elicited memory impairment and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and cognitive disorder by up-regulating the insulin receptor substrate-1 (IRS-1)/AKT and ERK/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways. Long-term HFFD-triggered neuroinflammation was restored by EGCG supplementation by inhibiting the MAPK and NF-κB pathways, as well as the expression of inflammatory mediators, such as TNF-α. EGCG also reversed high glucose and glucosamine-induced insulin resistance in SH-SY5Y neuronal cells by improving the oxidized cellular status and mitochondrial function. To our knowledge, this study is the first to provide compelling evidence that the nutritional compound EGCG has the potential to ameliorate HFFD-triggered learning and memory loss.-Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y., Gao, Y., Liu, X. EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.

EGCG ameliorates diet-induced metabolic syndrome associating with the circadian clock.

In response to the daily light-dark (LD) cycle, organisms on Earth have evolved with the approximately 24-h endogenous oscillations to coordinate behavioral and physiological processes, including feeding, sleep, and metabolism homeostasis. Circadian desynchrony triggered by an energy-dense diet rich in fats and fructose is intimately connected with a series of metabolic disorders. Previous studies revealed that (-)-Epigallocatechin-3-gallate (EGCG) could mitigate metabolic misalignment; however, only a few reports have focused on its potential effect on directly manipulating circadian rhythms to ameliorate metabolic syndrome. Our goal was to investigate the regulating effect of EGCG treatment on metabolic misalignment triggered by a high-fat and high-fructose diet (HFFD) associating with the circadian clock. Our results indicated that HFFD treatment partially exhibited poor circadian oscillations of the core clock gene and the clock-controlled gene in the liver and fat relative to the control group. EGCG administration may ameliorate the diet-dependent decline in circadian function by controlling the Sirt1-PGC1αloop, implying the existence of an EGCG-entrainable oscillator. Subsequently, reducing fatty acid synthesis and elevating ß-oxidation in the liver coupled with the increasing brown adipose tissue (BAT) energy expenditure observed in the EGCG group of mice prevented the adipocyte hypertrophy and fat accumulations common to BAT and white adipose tissue (WAT) derived from the HFFD mice. This study is the first to provide compelling evidences that EGCG may ameliorate diet-induced metabolic misalignment by regulating the rhythmic expression of the circadian clock genes in the liver and fat.

Integral Compensation Function Observer and Its Application to Disturbance-Rejection Control of QUAV Attitude.

Observer-based disturbance rejection holds substantial theoretical and practical relevance in the field of control engineering, with numerous variants of disturbance observers already schemed. Nevertheless, the criteria for accuracy and avenues for enhancement remain areas warranting further investigation. This article introduces an integral compensation function observer (CFO) featuring a novel structure and efficient utilization of information for estimating disturbances in n th-order uncertain systems. This approach enhances estimation accuracy by addressing the inherent limitations of the linear extended state observer (LESO), such as low order, lacking usage of information, nonconvergence, and limited bandwidth. Through the derivation and quantification of the disturbance sensitivity transfer function (DSTF), this study examines the disturbance sensitivities of the CFO, LESO, and an improved ESO (IESO). The findings indicate that the CFO elevates the estimable order of disturbance and surpasses both LESO and IESO in bandwidth and disturbance estimation accuracy. In evaluating both the estimation accuracy of disturbance of the CFO and the disturbance-rejection performance (DRP) of CFO-based control, nonlinear pole assignment controls (NPACs) employing 2nd/3rd-order CFO, IESO, LESO, and 4th-order CFO are implemented in the context of attitude control for a quadrotor unmanned aerial vehicle (QUAV) that is exposed to prearranged disturbance torques. The results illustrate that the CFO outperforms the IESO and LESO in terms of accurately estimating the prearranged disturbing torques. Furthermore, the recorded magnitudes of attitude in response to disturbances underscore the superior DRP of CFO-NPAC relative to IESO-NPAC and LESO-NPAC.

Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration.

Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis. Aberrant astrocytic OxPhos induces lipid droplet (LD) accumulation followed by neurodegeneration that recapitulates key features of Alzheimer's disease (AD), including synaptic loss, neuroinflammation, demyelination and cognitive impairment. Mechanistically, when FA load overwhelms astrocytic OxPhos capacity, elevated acetyl-CoA levels induce astrocyte reactivity by enhancing STAT3 acetylation and activation. Intercellularly, lipid-laden reactive astrocytes stimulate neuronal FA oxidation and oxidative stress, activate microglia through IL-3 signalling, and inhibit the biosynthesis of FAs and phospholipids required for myelin replenishment. Along with LD accumulation and impaired FA degradation manifested in an AD mouse model, we reveal a lipid-centric, AD-resembling mechanism by which astrocytic mitochondrial dysfunction progressively induces neuroinflammation and neurodegeneration.

Can dietary patterns prevent cognitive impairment and reduce Alzheimer's disease risk: Exploring the underlying mechanisms of effects.

Alzheimer's disease (AD) is one of the fastest growing cognitive decline-related neurological diseases. To date, effective curative strategies have remained elusive. A growing body of evidence indicates that dietary patterns have significant effects on cognitive function and the risk of developing AD. Previous studies on the association between diet and AD risk have mainly focused on individual food components and specific nutrients, and the mechanisms responsible for the beneficial effects of dietary patterns on AD are not well understood. This article provides a comprehensive overview of the effects of dietary patterns, including the Mediterranean diet (MedDiet), dietary approaches to stop hypertension (DASH) diet, Mediterranean-DASH diet intervention for neurological delay (MIND), ketogenic diet, caloric restriction, intermittent fasting, methionine restriction, and low-protein and high-carbohydrate diet, on cognitive impairment and summarizes the underlying mechanisms by which dietary patterns attenuate cognitive impairment, especially highlighting the modulation of dietary patterns on cognitive impairment through gut microbiota. Furthermore, considering the variability in individual metabolic responses to dietary intake, we put forward a framework to develop personalized dietary patterns for people with cognitive disorders or AD based on individual gut microbiome compositions.

Characterizing brain metabolic function ex vivo with acute mouse slice punches.

Mitochondrial dysfunction and metabolic reprogramming are implicated in a variety of neurological disorders. Here, we present a protocol that enables complex profiling of brain metabolic function using acute mouse brain slices ex vivo. Utilizing differential metabolic conditions, substrates, and inhibitors, this protocol can be broadly applied to determine metabolic shift or reprogramming upon genetic manipulations, pathological insults, or therapeutic interventions and could thus further the understanding of the dynamic role of energy metabolism in brain physiological function and diseases. For complete details on the use and execution of this protocol, please refer to Qi et al. (2021).

Mitochondria-Targeted Therapeutics for Alzheimer's Disease: The Good, the Bad, the Potential.

Significance: Alzheimer's disease (AD) is the leading cause of dementia. Thus far, 99.6% of clinical trials, including those targeting energy metabolism, have failed to exert disease-modifying efficacy. Altered mitochondrial function and disruption to the brain bioenergetic system have long-been documented as early events during the pathological progression of AD. Recent Advances: While therapeutic approaches that directly promote mitochondrial bioenergetic machinery or eliminate reactive oxygen species have exhibited limited translatability, emerging strategies targeting nonenergetic aspects of mitochondria provide novel therapeutic targets with the potential to modify AD risk and progression. Growing evidence also reveals a critical link between mitochondrial phenotype and neuroinflammation via metabolic reprogramming of glial cells. Critical Issues: Herein, we summarize major classes of mitochondrion-centered AD therapeutic strategies. In addition, the discrepancy in their efficacy when translated from preclinical models to clinical trials is addressed. Key factors that differentiate the responsiveness to bioenergetic interventions, including sex, apolipoprotein E genotype, and cellular diversity in the brain, are discussed. Future Directions: We propose that the future development of mitochondria-targeted AD therapeutics should consider the interactions between bioenergetics and other disease mechanisms, which may require cell-type-specific targeting to distinguish neurons and non-neuronal cells. Moreover, a successful strategy will likely include stratification by metabolic phenotype, which varies by sex and genetic risk profile and dynamically changes throughout the course of disease. As the network of mitochondrial integration expands across intracellular and systems level biology, assessment of intended, the good, versus unintended consequences, the bad, will be required to reach the potential of mitochondrial therapeutics.

ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism.

Alzheimer's disease (AD) risk gene ApoE4 perturbs brain lipid homeostasis and energy transduction. However, the cell-type-specific mechanism of ApoE4 in modulating brain lipid metabolism is unclear. Here, we describe a detrimental role of ApoE4 in regulating fatty acid (FA) metabolism across neuron and astrocyte in tandem with their distinctive mitochondrial phenotypes. ApoE4 disrupts neuronal function by decreasing FA sequestering in lipid droplets (LDs). FAs in neuronal LDs are exported and internalized by astrocytes, with ApoE4 diminishing the transport efficiency. Further, ApoE4 lowers FA oxidation and leads to lipid accumulation in both astrocyte and the hippocampus. Importantly, diminished capacity of ApoE4 astrocytes in eliminating neuronal lipids and degrading FAs accounts for their compromised metabolic and synaptic support to neurons. Collectively, our findings reveal a mechanism of ApoE4 disruption to brain FA and bioenergetic homeostasis that could underlie the accelerated lipid dysregulation and energy deficits and increased AD risk for ApoE4 carriers.

Cellular Specificity and Inter-cellular Coordination in the Brain Bioenergetic System: Implications for Aging and Neurodegeneration.

As an organ with a highly heterogenous cellular composition, the brain has a bioenergetic system that is more complex than peripheral tissues. Such complexities are not only due to the diverse bioenergetic phenotypes of a variety of cell types that differentially contribute to the metabolic profile of the brain, but also originate from the bidirectional metabolic communications and coupling across cell types. While brain energy metabolism and mitochondrial function have been extensively investigated in aging and age-associated neurodegenerative disorders, the role of various cell types and their inter-cellular communications in regulating brain metabolic and synaptic functions remains elusive. In this review, we summarize recent advances in differentiating bioenergetic phenotypes of neurons, astrocytes, and microglia in the context of their functional specificity, and their metabolic shifts upon aging and pathological conditions. Moreover, the metabolic coordination between the two most abundant cell populations in brain, neurons and astrocytes, is discussed regarding how they jointly establish a dynamic and responsive system to maintain brain bioenergetic homeostasis and to combat against threats such as oxidative stress, lipid toxicity, and neuroinflammation. Elucidating the mechanisms by which brain cells with distinctive bioenergetic phenotypes individually and collectively shape the bioenergetic system of the brain will provide rationale for spatiotemporally precise interventions to sustain a metabolic equilibrium that is resilient against synaptic dysfunction in aging and neurodegeneration.

Nobiletin Protects against Systemic Inflammation-Stimulated Memory Impairment via MAPK and NF-κB Signaling Pathways.

Neuroinflammation has been intensively demonstrated to be related to various neurodegenerative diseases including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). A natural polymethoxylated flavone, nobiletin (NOB) has been reported to alleviate oxidative stress, insulin resistance, and obesity. In this study, we evaluated the protection effects of NOB on neuroinflammation and memory deficit. Three-month mice were administrated with NOB by oral gavage every day for 6 weeks (100 mg/kg/day); subsequently mice were injected intraperitoneally with lipopolysaccharide (LPS) for 7 days. Results of behavioral tests revealed that NOB dramatically ameliorated LPS-triggered memory deficit regarding synaptic dysfunctions and neuronal loss. Also, NOB suppressed the microglial activation and proinflammatory cytokine secretion, such as COX-2, IL-1ß, TNF-α, and iNOS. Similarly, upon LPS stimulation, pretreatment NOB diminished the secretion of the proinflammatory cytokines in BV-2 microglia cells by exposure to LPS via modulating MAPKs, PI3K/AKT, and NF-κB signaling pathways. In addition, NOB alleviated LPS-amplified redox imbalance, disturbance of mitochondrial membrane potential (MMP), and dampening of the expression of protein related to mitochondrial respiration. The present study provides compelling evidence that NOB decreased LPS-stimulated neuroinflammation and memory impairment through maintaining cellular oxidative balance and blocking the NF-κB transcriptional pathway, illustrating that the nutritional compound NOB may serve as a potential approach to alleviate neuroinflammation-related diseases.

Tea polyphenols direct Bmal1-driven ameliorating of the redox imbalance and mitochondrial dysfunction in hepatocytes.

Circadian rhythms are intimately linked to cellular redox status homeostasis via the regulation of mitochondrial function. Tea polyphenols (TP) are nutraceuticals that possess powerful antioxidant properties, especially ameliorating oxidative stress. The objective of this study was to investigate whether circadian clock is involved in the protection effect of TP on oxidative stress cell models. TP ameliorate H2O2-triggered relatively shallow daily oscillations and phase shift of circadian clock genes transcription and protein expression. Meanwhile, TP attenuate H2O2-stimulated excessive secretions of reactive oxygen species (ROS) and restore the depletions of mitochondrial function in a Bmal1-dependent manner. Furthermore, TP treatment accelerates nuclear translocation of Nrf2 and modulates the downstream expressions of antioxidant enzymes. Intriguingly, knockdown of Bmal1 notably blocked Nrf2/ARE/HO-1 redox-sensitive transcription pathway. Our study revealed that TP, as a Bmal1-enhancing natural compound, alleviated redox imbalance via strengthening Keap1/Nrf2 antioxidant defense pathway and ameliorating mitochondrial dysfunction in a Bmal1-dependent manner.

EGCG evokes Nrf2 nuclear translocation and dampens PTP1B expression to ameliorate metabolic misalignment under insulin resistance condition.

As a major nutraceutical component of green tea (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists due to its well-documented antioxidant and antiobesity bioactivities. In the current study, we aimed to investigate the protective effect of EGCG on metabolic misalignment and in balancing the redox status in mice liver and HepG2 cells under insulin resistance condition. Our results indicated that EGCG accelerates the glucose uptake and evokes IRS-1/Akt/GLUT2 signaling pathway via dampening the expression of protein tyrosine phosphatase 1B (PTP1B). Consistently, ectopic expression of PTP1B by Ad-PTP1B substantially impaired EGCG-elicited IRS-1/Akt/GLUT2 signaling pathway. Moreover, EGCG co-treatment stimulated nuclear translocation of Nrf2 by provoking P13K/AKT signaling pathway and thus modulated the downstream expressions of antioxidant enzymes such as HO-1 and NQO-1 in HepG2 cells. Furthermore, knockdown Nrf2 by small interfering RNA (siRNA) notably enhanced the expression of PTP1B and blunt EGCG-stimulated glucose uptake. Consistent with these results, in vivo study revealed that EGCG supplement significantly ameliorated high-fat and high-fructose diet (HFFD)-triggered insulin resistance and oxidative stress by up-regulating the IRS-1/AKT and Keap1/Nrf2 transcriptional pathways. Administration of an appropriate chemopreventive agent, such as EGCG, could potentially serve as an additional therapeutic intervention in the arsenal against obesity.

EGCG stimulates the recruitment of brite adipocytes, suppresses adipogenesis and counteracts TNF-α-triggered insulin resistance in adipocytes.

The global rise in obesity and type 2 diabetes has precipitated the need for therapeutic intervention in the arsenal against adiposity. (-)-Epigallocatechin-3-gallate (EGCG), a major nutraceutical component of green tea, has been regarded as a nutraceutical that has powerful antioxidant and anti-obesity bioactivities. In the present study, we showed that EGCG alleviates intracellular lipid accumulation markedly, and the inhibitory effect was largely limited to the early stage of adipocyte differentiation. Consistently, EGCG notably evoked the phosphorylation of AMPK and ACC and blunted the key enzymes of de novo lipogenesis. Interestingly, EGCG elicited iWAT-preadipocyte-derived mature white adipocyte beiging via activating thermogenic gene Ucp1 expression and mitochondrial biogenesis. Furthermore, our results also revealed that EGCG attenuated insulin signaling pathway blockage induced by TNF-α through the abrogation of redox imbalance and mitochondrial dysfunction. These findings indicate that EGCG is capable of suppressing adipogenesis and evoking white adipocyte beiging and therefore it may potentially serve as a novel approach to combat obesity.