To date, numerous studies on the activation mechanism of BAT have been published. Under cold stimulation, the transcription factor proliferator-activated receptor (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator -1α (PGC-1α) can activate BAT to produce heat ^[1][55]. In the meantime, free fatty acids, which are hydrolysed in the lipid droplets of brown adipocytes in response to cold stimulation can not only promote the division of mitochondria but can also increase the uncoupling activity of mitochondria, leading to an increase in the thermogenic properties of BAT ^[2][56]. The BAT is an important organ for heat production and hydrolyses triglycerides in brown adipocytes mainly by β-oxidation in the mitochondria. As a result, the lipid droplets and mitochondria are necessary for BAT thermogenesis. Cold stimulation can activate BAT by releasing adrenaline through sympathetic nerves, increasing the thermogenesis and expression of lipid metabolism-related genes and promoting the subcutaneous accumulation of beige fat ^[3][57]. The effects of cold stimulation on the body have been reported in mice and humans ^[4][58]. Mice stimulated with cold at 10 °C for 2–6 h showed an increase in the scapular brown fat oxidation metabolism and body surface temperature, as well as the expression levels of mitochondrial and thermogenesis-related genes ^[5][59]. Moreover, after a healthy adult was exposed to 19 °C for 2 h, FDG-PET/CT (Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography) showed that FDG in the supraclavicular and paraspinal adipose tissue was significantly absorbed in adipose tissue in a specific area, representing BAT. Metabolic activity suggested that cold stimulation could induce and activate the adipose tissue browning, and the cold-induced absorption of supraclavicular fat FDG was significantly negatively correlated with BMI and visceral fat ^[6][60]. In addition, the cold or β-adrenoceptor agonists could stimulate the production of heat in humans and mice ^[7][61], and at the same time, induce FGF21 expression in adipose tissues. Fibroblast growth factor 21 (FGF21) regulates protein levels of PGC-1α at the post-transcriptional level and activates subcutaneous fat browning as well as thermogenesis of brown fat in mice ^[8][62]. FGF21-knockout mice showed impaired intolerance to cold and WFB ^[9][63]. By activating the β3 adrenergic receptor-cyclic adenylate-protein kinase, cold stimulation could activate a signalling pathway, which promoted the lipolysis of stored triglycerides to release free fatty acids and increase expression levels of thermogenesis-related genes ^[10][64]. A recent study reported that histone deacetylase 1 (HDACl) was a negative regulator of the brown fat thermogenesis. Cold exposure and β-adrenergic receptor activation could activate HDACl and brown fat-specific genes. In order to promote the expression of brown fat-specific genes, the subregions were separated ^[11][65]. Other regulatory factors are also involved in the adaptive thermogenesis induced by cold stimulation. Janus kinase2 (JAK2) is a signal transduction factor for various hormones and growth factors, regulating the development and function of fat. The JAK2 and UCP-1 were both elevated in cold-stimulated brown fat and the JAK2-knockout mice showed lower levels of brown fat marker genes and a lower core body temperature, indicating that this protein could also be an important part of the brown fat adaptive thermogenesis ^[12][66]. The transcription factors and their cofactors, including ATF2 (activating transcription factor) ^[13][67], Zfp516 (zinc finger protein 516) ^[14][68], and PGC-1α ^[8][62], are also involved in the regulation of cold-stimulated adaptive thermogenesis of adipose tissues.

Exercise can increase the number of brown fat progenitor cells and the expression level of the brown fat marker gene UCP-1. Simultaneously, exercise can also promote WFB ^[15][69], as evidenced by an increase in the number of white fat mitochondria and upregulation of UCP-1, PGC-1α, and Dio2 (Deiodinase Iodothyronine Type II) and other brown fat marker genes ^[16][70]. Exercise could promote the PGC-1α expression in muscles in both mice and humans, which can regulate the brown fat UCP-1 expression level and thermogenesis. As a result, the mice, overexpressing PGC-1α in skeletal muscle, have been frequently used as exercise models ^[17][33]. Exercise increases the expression of brown fat marker genes UCP-1 and CIDEA (cell death-inducing DNA fragmentation factor, alpha) in inguinal fat, indicating that it browns subcutaneous fat in mice.

In contrast, numerous studies have reported that exercise training in mice could promote the expression of brown fat-specific genes, such as UCP-1 in visceral fat but showed no effect on the subcutaneous fat. In addition, exercise induced WFB in mice was also affected by diet. The subcutaneous inguinal fat in the exercise mice showed a browning phenotype. The proteins involved in the thermogenesis and oxidation of adipose tissue, including PGC-1α, UCP-l, adipose triglyceride lipase (ATGL), adenosine monophosphate-activated protein kinase (AMPK) as well as increased phosphorylation and palmitate oxidation levels were observed. However, the exercise-induced browning phenotype decreased significantly in the high-fat diet (HFD)-fed mice ^[18][19][71,72].

In recent years researchers have found that High Intensity Interval Exercise (HIIT) has similar or better effects than continuous aerobic exercise in relieving symptoms of insulin resistance ^[20][73]. There is no clear definition of HIIT at this stage, but it generally consists of multiple repetitions of short or prolonged exercise at near or extreme intensity (85–95% VO2max or HRmax), interspersed with intervals ranging from a few tens of seconds to a few minutes ^[21][74]. Studies have shown that HIIT exercise can improve metabolic disorders in rodents, mainly by improving biological processes such as transmembrane transport of fatty acids and β-oxidation, with HIIT being significantly more effective than other forms of exercise ^[22][75]. Interestingly, HIIT also significantly promotes the expression of genes associated with white adipose browning in subcutaneous adipose tissue in mice, such as UCP-1, facilitating the transition from white to beige adipose tissue ^[23][76]. However, in a 12 week training study (30 min at 70% of maximal power output 2 times/wk) in obese or sedentary humans, this high intensity training and resistance training did not alter the expression of brown fat markers such as UCP-1 and Prdm16 in the adipose tissue of obese individuals ^[24][77]. However, there is controversy as to whether exercise at different intensities promotes beige-coloured white adiposity in humans. A study by Berenice et al. ^[25][78] showed that a 12 week bicycle-training program (3 times per week, intensity 70–80% HRmax) in people with different BMIs significantly promoted abdominal fat in the exercise group significantly promoted the expression of beige fat marker genes for abdominal fat in the exercise group. However, the results of Tsiloulis’ study showed that long-term endurance exercise training did not promote beige or brown abdominal fat in obese men ^[26][79]. The interspecies differences in the effects of exercise on adipose tissue browning in humans and rodents may be due to different patterns of adipose tissue gene expression between species, and the authors suggest that the small sample size of studies conducted on white fat browning in humans, the difficulty of collecting comprehensive subcutaneous adipose tissue from subjects, and the incomplete mapping of exercise intensity and duration of exercise have contributed to these interspecies differences. The results vary between species. Moreover, irisin plays an important role as a signalling molecule in the regulation of white adipose tissue browning during exercise, as described in detail in Section 4.4.8.

Brown fat plays an important biological role in the regulation of energy metabolism throughout the body, in addition to a similar role for white fat browning (beige fat). Therefore, activation of brown fat as well as beige fat thermogenesis is an excellent target for improving the body’s energy metabolic balance and promoting weight loss. ReIn thisearchers paper, we summarise data on small molecules of food origin that can modulate energy metabolism in obese patients by activating brown or beige fats. Furthermore, studies on mostly food-derived small molecules have only been conducted at the mouse level and have not been carried out in human populations for the time being. Therefore, further studies on the role of these small molecules in the regulation of beige fat and brown fat thermogenesis in humans are still needed.

Sesamol is a fat-soluble lignan compound, which is the main component of the sesame oil fragrance. In addition, sesamol is also a critical quality stabilizer for sesame oil with a wide range of biological activities, including anti-oxidation and scavenging of free radicals. Sesamol inhibits the white adipogenic genes, such as the mRNA levels of PPARγ, acetyl-coenzyme A carboxylase (ACACA), steroid regulatory element-binding protein 1c (SREBP-1c), and fatty acid synthase gene (FASN). It can also inhibit the increased number of lipid droplets in BAT and promote the expression of brown fat marker genes, including UCP-1, FGF21, and COXII ^[27][80]. Moreover, in-vitro studies reported that treating the 3T3-L1 model cells with a specific dose of sesamol could significantly inhibit the accumulation of lipid droplets in adipocytes ^[28][81].

Resveratrol (RSV) is an anthraquinone terpenoid. It was first discovered in the rhizomes of resveratrol by Japanese researchers in 1939 ^[29][82].

Resveratrol is widely distributed and biosynthesized by the plants in the free state as well as glycoside-binding state. It can activate Silent Information Regulator 1 (SIRT1) to play a similar role in the calorie restriction (CR) in various functions, such as the regulation of organism’s lifespan and inhibition of premature cell aging. Resveratrol inhibits the lipid peroxidation and lipoprotein modification caused by the reactive oxygen species (ROS) and affects the essential fatty acid metabolism.

Resveratrol is an agonist of SIRT1, increasing the cell viability and activity of the SIRT1 enzyme as well as their affinity for SIRT1-acetylated substrates ^[30][83]. Shi et al. ^[31][84] reported that the expression of SIRT1 was significantly higher in the WAT than that in the BAT and RSV could reduce the lipid accumulation by increasing the deacetylation of PPARr through SIRT1. Moreover, activated SIRT1 could deacetylate PGC1α to achieve the lipid glucose-lowering effect ^[32][85]. In addition, pterostilbene could also promote the WFB. In addition, the results of the study by Suo et al. ^[33][86] showed that long-term feeding of resveratrol to db/db mice significantly promoted lithocholic acid (LCA) in the plasma and faeces, thus indirectly promoting browning of white fat.

Furthermore, grape pomace extract (GPE), which is functionally like RSV is extracted from grape pomace as a residue in the winemaking process. The GPE is mainly composed of berry skins and seeds, containing a lot of phenolic compounds. The most abundant polyphenols, which are found in Malbec grape pomace, include flavanols (catechins, epicatechins, and proanthocyanidins), flavonols (quercetin), stilbene (RSV), and anthocyanins ^[34][87].

The GPE prevents the palmitate-mediated down-regulation of FNDC5/irisin protein expression and secretion by activating the PGC-1α. Circulating irisin can upregulate the expression of UCP-1 in WAT and promote the formation of brown-like adipocytes ^[35][88].

Ellagic acid is a phytochemical abundant in fruits and vegetables, in particular berries, with reported pharmacological effects, such as anti-oxidation and anti-cancer. In order to maintain cell viability, ellagic acid could inhibit the protein expression of cyclin A, thereby inhibiting the formation of fat in the 3T3-LI model adipocytes ^[36][89]. Ellagic acid could inhibit the accumulation of triglycerides in adipocytes by downregulating the expression of the key genes, such as PPARγ, and the transcription factor CCAAT-enhancer-binding protein α (C/EBPα). A study by Ning Chao ^[37][90] reported that the ellagic acid could inhibit the HFD-induced accumulation of lipids in rats as well as could down-regulate the expression levels of lipid synthesis-related proteins, such as PPARγ, C/EBPβ, and C/EBPα, and upregulate the BAT marker proteins UCP-1 and UCP-1 in WAT. The PGC-1a can inhibit the transformation of pre-adipocytes into mature adipocytes, thereby promoting the WFB. Yu et al. ^[38][91] reported that the pomegranate ellagic acid could promote lipid metabolism, reduce intracellular lipid levels, and inhibit the activities of lipoprotein lipase (LPL) and glucose-3-phosphate dehydrogenase (GPDH) thereby inhibiting the formation of fat in adipocytes, upregulating the PPARγ and adipocyte fatty acid-binding protein (aP2) levels, and down-regulating the obesity gene ob ^[37][90]. A study by Liu ^[39][92] suggested that the pomegranate ellagic acid could affect lipid metabolism mainly by inhibiting the gene expression of SREBP-1c and FASN, while promoting that of LPL, thereby inhibiting the lipid accumulation.

Flavan-3-ols are polyphenols found in many plant foods, such as cocoa beans, red wine, and apples, and are considered a mixture of catechins and B-type proanthocyanidins ^[40][93]. Previous studies reported that flavan-3-ols could play an essential role in the treatments of diabetes, cardiovascular disease, tissue damage, and inflammation, indicating their extensive role in the metabolism-related processes in the body and the maintenance of body homeostasis. Subsequent studies also reported their role in fat metabolism ^[40][93]. The treatment with flavan-3-ol could increase the sympathetic nerve activity, adrenaline contents, and the mRNA expression levels of UCP-1 in mice, suggesting that flavan-3-ol had a positive effect on lipid metabolism in mice, thereby affecting the proliferation and differentiation of brown adipocytes and related regulatory processes of WFB. Moreover, flavan-3-ols could also increase the concentration of catecholamines in plasma, which induce WFB by stimulating the activation of β-adrenergic receptors and mediating the protein kinase A signal transduction, thereby promoting the fat metabolism-related processes ^[41][94].

Catechin is a type of phenolic active substance extracted from natural plants, such as tea, and has various pharmacological activities, such as anti-tumour, anti-oxidation, and anti-bacterial activities as well as affects the heart and brain organs ^[42][95]. Epicatechin can induce WFB by promoting mitochondrial biogenesis, enhancing the mitochondrial structural and functional indicators, increasing the fatty acid metabolism, and upregulating the expression of BAT-associated genes. It can increase the expression levels of mitochondrial biogenesis-related proteins, such as PGC1α, mitochondrial transcription factor A (TFAM), SIRT1, SIRT3, and uncoupling protein 1 (UCP-1). Moreover, epicatechin can also activate the AMPK while enhancing the phosphorylation of ACC and inhibiting the expression of gluconeogenesis-related genes, which results in decreasing the fatty acid uptake and triglyceride synthesis, thereby inhibiting the lipogenesis, and increasing fatty acid oxidation. Epicatechin can activate the browning of adipose tissue and increase the cold-induced heat production in human body. It positively affects the browning of fat cells and WATs ^[43][96]. Therefore, this phytochemical has become a potential candidate for combating obesity.

Capsaicin is an alkaloid derived from pepper, which can bind to the vanilloid receptor subtype 1 (VR1) of sensory neurons in the mammals and produce a burning sensation. Capsaicin has been reported to lower blood pressure and cholesterol levels, prevent heart diseases, promote muscle growth, inhibit muscle atrophy, and can widely be used in food additives, medicine, and health care ^[44][97]. Capsaicin induces WATB and fights obesity by activating the TRPV1 (transient receptor potential cation channel, subfamily V, member 1) channel-dependent mechanism in obesity treatment ^[45][98]. Specifically, the TRPV1 channel-dependent increase in the intracellular Ca²⁺ and phosphorylation of Ca²⁺/calmodulin-activated protein kinase II and AMP-activated kinase promote the expression and activity of SIRT1, thereby triggering the WFB. Capsaicin can regulate the PPAR transcription, upregulate the specific BAT- and WAT-associated gene, stimulate SIRT1-dependent deacetylation of PPARγ and transcription factor Prdm16, and promote the interaction between PPARγ and Prdm16, thereby leading to WFB.

Curcumin is a diketone compound extracted from the rhizomes of the families Zingiberaceae and Araceae. It has a wide range of biological activities, including anti-inflammatory, antioxidant, lipid-regulating, anti-viral, anti-infective, anti-tumour, and anti-coagulation activities. It has also a wide range of pharmacological activities, such as anti-liver fibrosis and anti-atherosclerosis ^[46][99]. In the fat-related processes, curcumin could also reduce body weight and fat mass, by promoting the production of beige fat cells and expression of heat-producing genes and increasing the mitochondrial biogenesis, without affecting the food intake in mice. The cold tolerance studies in rats ^[47][100] reported that curcumin could promote the expression of β3AR gene in the inguinal white adipocytes, thereby increasing the norepinephrine level in plasma and inducing the WFB ^[48][101]. In addition, curcumin could also induce the polarization of M2 macrophages by secreting interleukins IL-4 and IL-13, which could cause WFB ^[49][102].

Berberine, also known as berberine, is a quaternary ammonium alkaloid, which is isolated from the traditional Chinese medicine Coptis Rhizoma. It is the main effective component in the anti-bacterial activity of Coptis. As one of the effective anti-bacterial and antitoxic substances, it has a widespread clinical use ^[50][103]. Berberine has metabolic regulatory roles as well, such as a role in the anti-oxidation, anti-inflammatory, anti-tumour, anti-bacterial, liver protection, neuroprotection, hypolipidemic, and hypoglycaemic pathways ^[51][104]. Studies generally believe that Berberine could increase the energy expenditure in obese db/db mice, limit their weight gain, and improve insulin sensitivity, cold tolerance, and the activity of BAT. Berberine increases the expression of thermogenic genes, including UCP-1, the WAT, BAT, and primary adipocytes, through the mechanisms, involving AMPK and PGC-1α. In order to induce the brown/beige lipogenesis, berberine could increase the transcription of PRDM16 by increasing the demethylation of the active promoter region of PRDM16 gene, which is a main regulator in the browning process ^[52][105]. In summary, berberine could enhance the thermogenesis of brown adipocytes and WFB to promote the metabolic process of adipose tissue through the AMPK pathway, thereby showing its potential therapeutic significance for the treatment of obesity.

Quercetin is widely distributed in the stem bark, flowers, leaves, buds, seeds, and fruits of many plants and is mostly present in the form of glycosides ^[53][106]. It has a wide range of biological activities, such as tissue anti-oxidation ^[54][107], anti-cancer ^[55][108], anti-bacterial, anti-inflammatory ^[56][109], anti-allergic, and antidiabetic activities ^[57][110], as well as a strong biological and therapeutic effect on cardiovascular diseases ^[58][111]. In order to the improve obesity, studies have reported that quercetin could reduce lipid deposition in the liver and the storage of WAT in the HFD-fed mice, thereby lowering the triglycerides contents in plasma and reducing their weight ^[59][112]. In the process of WFB, quercetin increased the expression levels of UCP-1 and brown fat marker fatty acid elongase 3 (Elovl3). The specific mechanism involves the quercetin/AMPK/SIRT1/PGC1α pathway, directly acting on the adipocytes and increasing the mitochondrial biogenesis to induce browning ^[60][113]. Interestingly, quercetin is also known as phytoestrogens due to its ability to bind to the oestrogen receptor (ER). Studies have shown that the mouse ER-β ligand LY3201 could induce WFB by directly regulating the sympathetic ganglia and adipocytes, increasing oxygen consumption, and reducing the body weight ^[61][114]. Therefore, the effect of quercetin to induce browning in humans and improve the triglyceride metabolism should be further investigated.

Fucoxanthin is a natural pigment of xanthophylls in carotenoids in brown algae, diatoms, golden algae, and yellow-green algae. It has anti-tumour, anti-inflammatory, antioxidant, and anti-obesity effects as well as protective effects in nerve cells. It is widely used in the medicines and skincare, beauty products, and health care products ^[62][115]. Fucoxanthin can improve insulin resistance and lower blood sugar levels ^[63][64][116,117]. In a subsequent experiment, an increase in the intake of fucoxanthin in mice increased the mRNA expression levels of β3-AR in WAT, which might stimulate the sympathetic nervous system and upregulate the expression of UCP-1, thereby generating heat ^[65][118]. Studies have found that, in rodents, the anti-obesity effects of fucoxanthin were related to the activation of brown fat and WFB. However, fucoxanthin and its metabolite fucoxanthin neither induced the browning of human adipocytes nor changed the mRNA expression levels of PGC-1α, PPARα, PPARγ, PDK4, and FAS ^[66][119]. Therefore, the clinical use of fucoxanthin as a drug to treat obesity requires further studies.

This is a terpenoid organic compound, which is extracted from the leaves and stems of peppermint ^[67][120]. It is used as a stimulant in medicine and acts on the skin or mucous membranes, showing cooling effects and relieving itching. It can be taken orally as an expel medicine for headaches or the inflammation of nose, pharynx, and throat. It can also be used as a flavouring agent in toothpaste, perfume, beverages, and candies. Studies have shown that inducing the transient receptor potential cation channel, subfamily M, member 8 (TRPM8) activation by dietary menthol might enhance the WFB and improve the diet-induced obesity. The TRPM8 is an ion channel, which can detect cold stimuli in the thermal sensory system. Its activation can upregulate the expression levels of UCP-1 and PGC-1α, thereby enhancing the lipid metabolism. Menthol could also increase the levels of iron and copper in adipose tissue by activating the TRPM8. The concentration of related metals in adipose tissues is closely related to the health and differentiation of adipose tissues and WFB ^[68][121]. Iron and copper are the essential components of the inner membrane complex of mitochondria, which constitute the electron transport chain. Therefore, these metals might participate in the energy metabolism by playing a role in mitochondria and BAT activation. In summary, TRPM8 might participate in WFB by increasing the expression levels of thermogenesis- and metabolism-related genes. As an activator of TRPM8, menthol might be a promising candidate for the treatment of obesity and other metabolic diseases.

Chlorogenic acid, a common phenolic acid, is found in fruits, vegetables, and traditional Chinese medicines and is responsible for a variety of physiological activities. It is also one of the main anti-bacterial and anti-viral pharmacological components of the honeysuckle. Although it has a wide range of anti-bacterial activities, it causes sensitivities among some people ^[69][122]. Chlorogenic acid could attenuate the high-carbohydrate and HFD-induced cardiovascular and liver metabolic disorders in rats caused by showing anti-obesity effects. It could also stimulate the production of brown fat cells by promoting the glucose uptake and mitochondrial function ^[70][123]. Furthermore, to induce WFB, chlorogenic acid and caffeic acid could act synergistically and activate the browning program in human adipocytes by upregulating the expression of AMPK and other browning-associated genes at the transcription and protein levels. Chlorogenic acid could exert anti-diabetic and anti-obesity effects through the AMPK pathway, enhance the expression levels of PPARγ, PRDM16, and PGC-1α in BATs and WATs, increase the insulin production, and inhibit key enzymes in lipid biosynthesis ^[71][124].

Chrysin is a flavonoid compound, which is extracted from plants in the Bignoniaceae family, which has anti-oxidation, anti-tumour, anti-cancer, anti-viral, anti-hypertensive, anti-diabetic, anti-bacterial, anti-allergic, and other pharmacological and physiological activities. Moreover, these compounds are widely distributed in plants and have relatively low toxicity and high biomedical research potential ^[72][125]. The WFB potential of chrysin has attracted great attention. Chrysin can regulate fat cells by reducing adipogenesis, increasing fat oxidation, and inducing browning ^[73][126]. Activation of AMPK in 3T3-L1 cells by increasing the expression of p-AMPK, chrysin could significantly upregulate the expression of PGC-1α, UCP-1, PRDM16, PPAR family proteins, and other browning proteins in the 3T3 model cells, thereby promoting the lipolysis, fat oxidation, and thermogenesis and reducing the fat production. Chrysin can also stimulate the expression of perilipin (PLIN) which inhibition of lipolysis in the presence of PKA stimulation and enhancement of lipolysis in the presence of PKA stimulation. A study reported that the increased expression of PLIN was a cause of the anti-obesity effects of chrysin and recruitment of brown adipocytes to the white adipocytes ^[74][127]. The in vitro data obtained from the 3T3-L1 adipocytes showed that chrysin could significantly induce the fat browning. However, its role in the body remains to be explored.

Cinnamic aldehyde is an organic aldehyde compound, which is abundantly present in the Sri Lankan cinnamon oil, ageratum oil, hyacinth oil, rose oil, and other cinnamon plants ^[75][128]. Cinnamic aldehyde induced the browning of WATs in the HFD-fed mice and showed therapeutic efficacy in obesity. The cinnamic aldehyde treatment specifically reduced the body weight, fat mass, food intake, serum lipid, free fatty acids, and leptin levels ^[76][129]. It also improved insulin sensitivity in the HFD-induced obese mice, thereby reducing the insulin resistance in obese mice ^[77][130]. In addition, it can also inhibit the hypertrophy of adipose tissues and induce the browning of WATs and UCP-1 expression. Furthermore, it could enhance the expression of PPARγ, PRDM16, and PGC-1α proteins in the WATs and BATs, increase the mitochondrial respiration and enhance lipid metabolism ^[78][131]. Cinnamic aldehyde might play a role in the treatment of obesity and other related diseases in the future, but its potential mechanism is needed to be investigated.

Luteolin is a natural flavonoid compound, which is abundantly present in various edible and medicinal plants, such as pepper, celery, thyme, mint, honeysuckle, etc. A recent study showed that dietary luteolin improved the diet-induced obesity and insulin resistance in mice ^[79][132].

Luteolin promoted the browning of differentiated primary brown cells and subcutaneous adipocytes by regulating the AMPK/PGC1α pathway. The luteolin treatment increased the protein levels of UCP-1, PGC1α, and SIRT1 and the phosphorylation levels of AMPKα and ACC. In addition, luteolin could also induce the beige cell-specific markers in the differentiated primary subcutaneous adipocytes ^[80][133]. At present, studies have reported that dietary luteolin could enhance the activity of brown adipocytes, formation of beige adipocytes and related thermogenesis processes, and improve the diet-induced obesity and insulin resistance ^[80][133].

Taurine is a sulphur-containing amino acid in animals (a nonprotein amino acid), which is synthesized from methionine and cysteine. Studies have shown that taurine can participate in various biological and physiological functions, including membrane stabilization, salt coupling, immune regulation, and anti-oxidation ^[81][134]. In a recent study, taurine treatment could induce the browning of WAT, which depended on the mRNA induction of PGC1 in WATs mediated by the AMPK signal. The results showed that taurine could play an essential role in regulating the production of adipose tissues and plasticity of white fat on BAT and provide a mechanism for the protective effects of taurine on obesity ^[82][135].

Emodin is a natural anthraquinone derivative and has various pharmacological effects, including the lowering of blood lipids and regulation of glucose utilization (in the rodent model species) ^[83][136]. Emodin significantly increased the mRNA expression levels of beige adipocyte markers, such as Cd137, Tmem26, and Tbx1 in inguinal white adipose tissue (iWAT), and UCP-1, CD36, FABP4, and PPARα as well as the expression level of inhibitory protein expression in both the iWAT and BAT. Studies reported that emodin could improve the obesity and metabolic disorders in obese mice. In addition, it could also promote browning in the iWAT and activate BAT activity ^[84][137]. In addition, the changes in lipid contents in the iWAT and BAT caused by emodin treatment were highly specific to certain molecular lipid species, indicating that the changes in the tissue lipid contents reflected the selective remodelling of iWAT and BAT by glycerophospholipids and sphingolipids in response to the emodin treatment.

3′-Hydroxydaidzein (OHD) is a daidzein metabolite (DAI), which is present in the fermented soy products, such as miso. The DAIs have been reported to affect the lipid accumulation, but the effects of OHD on lipid accumulation require further investigations. A study investigated the effects of OHD on the HFD-induced obese. The results showed that as compared to the HFD group, the mice treated with 0.1% OHD (HOHD) showed significant reduction in their body weight and groin fat without changing their food intake. Hyperlipidaemia in the HOHD and DAI groups was relieved by lowering the serum levels of triglyceride and total cholesterol. As compared to the HFD group, the HOHD and DAI groups showed significantly smaller size of the fat cells in the inguinal as well as increased expression levels of the PRDM16, C/EBPβ, p-p38, SIRT1, PGC1α, and UCP-1 proteins. In addition, the gut microbiota of the mice was enriched with Lachnospira and GCA_900066225 in the OHD and DAI groups as compared to the HFD group. In conclusion, OHD could improve the HFD-induced obesity in mice by stimulating the browning of WAT and regulating the gut microbiota ^[85][138].

Rice bran is a nutrient-rich and resource-rich by-product, which is produced during the processing of rice grains and accounts for about 10% of the rice weight. It has vital health-promoting effects, including anti-cancer, anti-obesity, anti-diabetics, anti-dyslipidaemia, and anti-inflammatory activities ^[86][139]. The oral administration of rice bran could also significantly upregulate the expression level of UCP-1 protein and coding genes and downregulate those of TCF21 and HOXC8 (WAT-specific proteins). In addition, RRB IRB and is also effectively increased PRDM16 and PGC-1α expression ^[87][140].

Purple Sweet Potato is a functional food rich in anthocyanins, having various potential biological and pharmacological effects. As compared to the HFD control mice, the PSP-treated mice showed a significant upregulation of browning-related gene expression, including PGC1α and UCP-1, in the iWAT. Similarly, in the mouse adipocytes treated with PSP, the protein levels of PGC1a and UCP-1 increased. These results indicated that PSP might regulate the energy expenditure by regulating these molecules promotes browning of white adipose tissue and prevent the HFD-induced metabolic abnormalities ^[88][141].

In addition to the above nutrients, numerous studies have shown that the dietary apple polyphenols ^[89][142], strawberry methanol extract ^[90][143], dietary silk peptides ^[91][144], Lactobacillus amylovorus KU4 ^[92][145], chitosan and chito-oligosaccharides ^[93][146], Sargassum ^[94][147], freeze-dried Aristotelia chilensis berries ^[95][148], cardamom ^[96][149], psoralen seeds prenylated flavonoid standardized extract ^[97][150], fermented Cordyceps militaris extract ^[98][151], genistein ^[99][152], broccoli ^[100][153], and allicin ^[101][154] could also induce the browning of WATs.

The above molecules of dietary origin may be one of the dietary components of obese individuals with disorders of glucolipid metabolism that reverse obesity by stimulating thermogenesis in brown or beige adipose tissue. In this section, reswearchers also summarise the molecular mechanisms regarding the contribution of various molecules of dietary origin to the stimulation of WFB. First, capsaicin ^[45][98], epicatechin ^[43][96] and quercetin ^[57][110] promote WFB by activating the cAMP signalling pathway. Curcumin ^[49][102] and fucoxanthin ^[66][119] promote white adipose tissue browning by enhancing the expression of the β3AR gene in white adipose tissue, thereby mimicking the effect of cold stimulation. In addition, the secretion of cytokines that promote thermogenesis in brown fat is also an important way for dietary molecules to regulate white adipose tissue browning, such as chlorogenic acid ^[69][122], chrysin ^[74][127], lignan ^[102][155] and taurine ^[82][135]. The above nutrients suggest to researchers that dietary modulation of the metabolic syndrome in obese individuals may become one of the future treatments for obesity. However, relying solely on the findings of the current phase of research is not sufficient. Many of these nutrients have been studied at the in vitro level, with studies using mouse 3T3-L1 as a model, but the changes in gene expression data at the cellular level are not sufficient to demonstrate similar results in human cell lines or even in humans. Furthermore, such studies of white fat browning at the cellular level do not demonstrate whether a nutrient is toxic to other tissues and organs in mice or humans. In addition, some nutrients have been tested for in vivo functional validation in rodents. However, in the case of resveratrol, for example, it is high doses of resveratrol that promote white fat browning. However, long-term high dose administration of resveratrol is not feasible for humans. Furthermore, because the AMPK signalling pathway is involved in a very wide range of biological processes in the human body, it is impractical to use AMPK agonists in humans to activate brown, beige adipose tissue for thermogenesis. More importantly, subcutaneous fat as well as visceral fat is more susceptible to browning in rodents than in humans. Therefore, more needs to be reported on the molecular mechanisms and safety of dietary molecules for the treatment of obesity metabolic syndrome through a particular dietary molecule or dietary combination as a dietary therapy.