INTRODUCTIONThe adipose tissue (AT) tissue is a form ofconnective tissue, the cells of which are filled with a fatdrop [1]. AT is distributed throughout the body and playsthe key role in the body energy homeostasis as a lipidreservoir. Moreover, adipocytes are endocrinologicallyactive, especially visceral [2, 3]. The content of adiposetissue and its lipid composition is strongly depended onbiological species, diet, climate, etc.Historically, adipose tissue of mammals has beendivided into two types, white adipose tissue (WAT)and brown adipose tissue (BAT) based on its visibledifferent color, as well as on its different physiologicalfunctions [4]. Anatomically, WAT presented in twomajor depots, subcutaneous and visceral around internalorgans and comprises the largest AT volume in mostmammals [2, 4, 5]. WAT is specialized in handlingfatty acids and triglycerides (TGs) and critical forenergy storage, endocrine communication, and insulinsensitivity [4, 5]. In contrast, amount of BAT is stronglylower. BAT participates in non-shivering thermogenesisand largely present in mammals postnatally andduring hibernation [2, 4]. Although BAT is readilyobserved in both infant and adult mammals, BATis gradually replaced by WAT with aging [2]. Beigeadipose (BeAT) tissue is the third type of AT andis a result of “browning” of WAT, when brown-likeadipocytes appear at anatomical sites characteristic ofWAT [6]. It is also called Brite (brown-in-white) [7, 8].Originally, BeAT was observed to arise in response to11Chernukha I.M. et al. Foods and Raw Materials, 2022, vol. 10, no. 1, pp. 10–18cold exposure; however, such factors, as diet, physicalactivity, pre-and probiotics, pharmaceutical and plantbasedsubstances, etc. can also induce “beigeing” or“browning” of WAT [9].Health status, survival of offspring, quality of pigprocessing products are strongly depended on proportionof all three types of AT. This article offers a review ofstructural and functional specificity of white, beigeand brown adipose tissue, as well as possibility of itsformation and divergence in pigs.RESULTS AND DISCUSSIONCharacteristics of white, beige and brown adiposetissue. The general classification of adipose tissue isbased on color of AT, which is corresponded to lipidcontent, mitochondrial density and vascularization(Fig. 1). White adipocytes contain a single lipid dropletoccupying approximately 90% of the cell space [9]. BATis highly vascularized, brown adipocytes contain a largenumber of mitochondria, but lipid droplet is smaller andpresented in multiple vacuoles [9, 10]. Beige adipocytesdisplay characteristics of both brown and white fat cells,the content of mitochondria is higher than in WAT, lipiddroplet is not a single, but bigger than in BAT [9].Canonically, adipocytes are different in the originand thought to arise from the de novo differentiationof precursor cells, particularly, white adipose stemcells originate from Myf5 (myogenic regulatory factor)negative progenitors, whereas brown adipose stemcells originate from myogenic lineage and expressMyf5 [12, 13]. Othervise, adipose precursors areheterogeneous, and the exact precursor population foradipogenesis may depend on the sex, location, age, orproadipogenic stimulus [14]. However, more than 95%of the precursors in brown fat are labeled with Myf5-Cre [15]. Beige adipocytes appears in WAT duringwhite to brown transdifferentiation or can arise fromadipogenic precursor cells in WAT through de novodifferentiation. Additionally, preadipocytes in WATgive rise to mature white adipocytes with the potentialto become brite adipocytes at a later point of time,White adiposetissue (WAT)which confirmed that after repeated stimuli most briteadipocytes localize to the same patches within the depotafter the first stimuli. Such microenvironment factor, asdensity of vascularization, the types of stromal-vascularcells in the adipocyte’s vicinity, the composition of theextracellular matrix, and the local innervation could alsoinfluence on this process [12, 16, 17].Different morphology of adipose tissues typescorresponds to other divergences, which is summarizedin Table 1. White adipose tissue (WAT) mainlymaintains energy homeostasis and stores energy inthe form of TGs, which are broken down into FFAand glycerol with following catabolism to generateenergy when energy demands [10]. It also offersmechanical protection for muscles and internalorgans has an important role in conservation of bodytemperature [18]. Thus, subcutaneous WAT acts as ashock absorber, providing padding at various anatomicsites, whereas omental WAT is one of the visceral ATdepots, surrounding and protecting inner organs fromphysical injury [19]. Subcutaneous WAT is more proneto expansion and represents a physiological buffer forexcess energy intake during times of limited energyexpenditure. When this storage capacity is exceeded,fat begins to accumulate ectopically in areas outsidethe subcutaneous WAT [19, 20]. Some WAT has onlybiomechanical function, such as infrapatellar AT,which preserves even upon extreme starvation [21].WAT is also known as an endocrine organ, especiallyvisceral, by producing adipokines, involving in lipidmetabolism or transport, immune system, regulationof pressure, blood coagulation, glycemic homeostasis,angiogenesis, etc. [18, 22]. Adipose tissue also expressesreceptors for most of these factors that are implicatedin the regulation of many processes including foodintake, energy expenditure, metabolism homeostasis,immunity and blood pressure homeostasis. Both visceralfat and subcutaneous adipose tissue produce uniqueprofile of adipocytokines, but visceral fat appears to bemore active [23]. Excess of WAT is strongly correlatedwith obesity and insulin resistance [24]. Exceeded fataccumulation in areas outside the subcutaneous WAT,such as lipid accumulation in ectopic tissues (liver,skeletal muscle, and heart) as well as in the visceraldepots lead to local inflammation, metabolic disordersand obesity-driven insulin resistance (IR) in WAT, liver,and skeletal muscle [25].Brown adipose tissue (BAT) was identified asa thermogenic organ in 1961, in 1978 BAT wasshown to be the major site of thermoregulatory nonshiveringthermogenesis [33]. However, beneficialeffects of BAT could be also explained with itsendocrine role through the release of endocrine factors,especially under conditions of thermogenic activation,such insulin-like growth factor I, interleukin-6,or fibroblast growth factor-21, which improveglucose tolerance and insulin sensitivity mainlyby influencing hepatic and cardiac function [34].Comparatively large amounts of BAT are present inNucleus Lipid droplet MitochondriaBeige (Brite) adiposetissue (BeAT)Brown adiposetissue (BAT)Figure 1 Comparison of white adipocytes, beige adipocytesand brown adipocytes in morphology [11]12Chernukha I.M. et al. Foods and Raw Materials, 2022, vol. 10, no. 1, pp. 10–18the newborns, and then reduced during aging [35].There is a the general proposal that brown adiposetissue is rapidly lost postnatally, the implication beingthat this process is normally concluded within the first(few) years of life, and that humans later in life do notpossess more than vestigical amounts of brown adiposetissue [36]. BAT contains a lot of mitochondria, freefatty acids serve as substrates for lipid oxidation andas potent activators of the mitochondrial uncouplingprotein 1 (UCP1) – the crucial trans-membrane proteinwhich catalyzes heat production at the mitochondriallevel [37]. UCP1 is the only memberable to translocateprotons through the inner membrane of brown adipocytemitochondria, uncouples respiration from ATP synthesisand therefore provokes energy dissipation in the formof heat while, also stimulating high levels of fatty acidoxidation. UCP1 homologs were identified but theyare biochemically and physiologically different fromUCP1 [38]. The biochemical activities and biologicalroles of the identified UCP2 and UCP3 are poorlyunderstood [39]. UCP2 is widely expressed in tissuesand cell types, could have particular importance inthe regulation in lipid metabolism and contribute toresting metabolic rate, fat oxidation, while UCP3could transport protons with a rate comparable toUCP1 [40–42]. Thus, it was shown that UCP3 ishighly abundant in BAT and the sensitivity of theprotein expression to temperature is similar to thatof UCP1 [43]. It was also revealed that UCP3 isexpressed in both skeletal muscle and brown adiposetissue may act as an inducible thermogenin in vivo,could indirectly mediate thermogenesis by increasingfatty acid oxidation and metabolite transport [44].However, UCP2 and UCP3 are not generally responsiblefor adaptive thermogenesis, but nonetheless they mayTable 1 Characteristics of white, beige and brown adipose tissueWhite adipose tissue (WAT) Beige (Brite) adipose tissue (BeAT) Brown adipose tissue (BAT) Ref.Function Storage of energyand endocrine tissueAdaptive thermogenesis Heat productionand endocrine tissue16,26–29Mitochondria Low, thin, elongated Present (upon stimulation) Abundant, bigger in sizeand contain more cristaeUncoupling protein Nearly undetectable Present (upon stimulation) PresentIron content Low Upon stimulation (Abundant) AbundantCorrelation withinsulin resistancePositive Negative NegativeVascularization Low High upon stimulation HighLipid composition High level of TGs, DGsDecreased fractionsof phosphatidylcholine(PC) andphosphatidylethanolamine(PE), with longer (C > 36)and more polyunsaturatedspecies, as well as lowerlevels of cardiolipin (CL)Higher contents of phosphatidylethanolamine (PE) andphosphatidylcholine (PC) fractions, with longer (C > 36) and morepolyunsaturated species, as well ascardiolipin (CL), lyso-PC (LPC)Higher abundance of phospholipids such as PEs and PCs(predominantly composed by polyunsaturated LCFAs,especially DHA)Higher in FFAs30, 31Thermogenicmechanisms– UCP1-independent(Ca2+cycling, creatine cycling)UCP1-dependent creatinecycling32be significantly thermogenic when fully activatedby endogenous or exogenous effectors [45]. BAThas negative correlation with obesity and insulinresistance, increasing BAT mass could improve glucosemetabolism and metabolic health [46]. Thus, it wasestimated that 50 g of BAT can burn as much as 20%of daily energy intake; therefore even though the BATdepots are present in small amounts, the activatedtissue has the potential to substantially contribute toenergy expenditure. In addition to using lipids, BATalso displays a very high rate of glucose uptake undercold exposure, glucose uptake increases by 12-folds,dissipating energy as a function of increased bloodflow [47].Beige – brown in white or brite (BeAT) – anintermediate type of fat, which is similar functionally tobrown fat – it has a high thermogenicity and contains asignificant number of mitochondria. Nevertheless, beigeadipocytes may secrete certain factors that affect WATfunction, systemic metabolism or both, has negativecorrelation with obesity and insulin resistance andappears upon the stimulation into WAT [29, 48, 49].BeAT plays the key role in adaptive thermogenesis,subcutaneous WAT is particularly prone tobrowning [50]. Thermogenic capacity of beige fat cellsdependents on the presence of UCP1 [51].Localization of beige and brown adiposetissue. Distribution of BAT and BeAT is different,localization is various in species; it is most studiedin humans and rodents (Fig. 2). In human infantBAT is located in interscapular and peri-renal areas,while in adults smaller BAT depots are located inthe anterior cervical, supraclavicular, axillary, periaortic,paravertebral and suprarenal regions, whilebeige fat signature could be formed in supraclavicular,13Chernukha I.M. et al. Foods and Raw Materials, 2022, vol. 10, no. 1, pp. 10–18Anterior cervicalSupraclavicularSuprascapularAxillaryInfrascapularInterscapularPeriaorticParavertebralabdominal visceral and subcutaneous fat depots [32,48, 52–57]. However, distribution of human BATcould be wider. Visceral BAT includes perivascular(aorta, common carotid artery, brachiocephalic artery,paracardiac mediastinal fat, epicardial coronary arteryand cardiac veins, internal mammary and the intercostalartery and vein), periviscus (heart, trachea and majorbronchi at lung hilum, esophagus, greater omentum,transverse mesocolon) and around solid organs(thoracic paravertebral, pancreas, kidney, adrenal, liver,hilum of spleen). Subcutaneous BAT includes depotslying between the anterior neck muscles and in thesupraclavicular fossa, under the clavicles, in the axilla,in the anterior abdominal wall, and in the inguinalarea [58]. Beige fat is could be also detected in cervical,parasternal, supraclavicular, para- and prevetebralareas [59].In mouse BAT is located in anterior cervical,supraclavicular, axillary, interscapular, infrascapular,paravertebral and perirenal areas, while BeAT – inanterior subcutaneous WAT, supraclavicular WATand inguinal WAT [32, 54, 56]. The main differencesbetween human and mouse adipocytes are defined.Human BAT are dispersed and represented a mix ofwhite, classical brown, and recruitable brite adipocytes,while murine the main BAT depots are in well-definedanatomic sites and homogeneously composed of brownadipocytes [60].The ways of “browning” of white adipose tissue.Beige adipocytes were originally observed to arise inresponse to cold; however, studies have since identifiedthat diet, exercise, pre-and probiotics, pharmaceuticalagents, numerous plant-based bioactives, and evenadipokines, can also induce “beigeing” or “browning”of WAT [61]. Thus, “beigeing” or “browning” of WATcould be caused by β-3 adrenergic receptor agonists,(CL 316243, BRL 26830A), short-chain fatty acids(acetate), dietary factors and organic compounds(capsaicin (and related capsinoids), plant-producedFigure 2 Localization of beige and brown adipose tissuein human and mouse [32, 52–55]Anterior subcutaneousAbdominal visceralAbdominalsubcutaneousPerirenalInguinalInterscapularPerirenalresveratrol, plant-derived berberine (BBR), fish oil,decaffeinated green tea extract, cinnamon extract,ginsenoside Rb1, curcumin, quercetin, ginger extract),nuclear receptors and ligands (farnesoid X receptor, liverX receptors), microRNAs (miRNA-32, miRNA-455),drug agents (Thiazolidinediones, Prostaglandin E2,Gleevec, Beta-lapachone, Slit 2 derived secretoryproduct, Artepillin C, Adrenomedullin 2), inflammatoryfactors (IL-6, IL-4, IEX-1), hormonal factors(thyroid hormones, Glucagon-like peptide 1, leptin,melatonin, natriuretic peptides), genetic factors(PTEN, Cox2, Foxc2, folliculin, Gq, TGF-β/Smad3),batokines (FGF21, apelin), exercise, PPAR agonists(rosiglitazone,WY14643), bone morphogenetic proteins(BMP7, BMP4), metabolites (lactate, β-hydroxybutyrate,beta-aminoisobutyric acid (BAIBA), retinoic acid),bariatric surgery (physical reconstruction of thegastrointestinal tract) [10, 49].Nevertheless, the most studied factor is coldexposure. Thus, exposure to cold sensed by the skin andcentral signals result in increased noradrenaline releasevia sympathetic neurons and subsequent stimulation ofvarious subtypes of β-adrenergic receptors (ADRBs,mainly subtype β3) and downstream cyclic adenosinemonophosphate signaling, leading to the proliferationof brown adipocytes and activation of lipolysis and/orof thermogenesis [62–64]. However, cold-induced BATfrom adult human neck area consists of classical brownadipocytes, as well as activated thermogenic fat in thesupraclavicular region is composed of both classicalbrown and beige adipocytes [65].Nutritional induction is also studied. WAT contentis influenced by n-3 PUFA, polyphenols, vitamin D,vitamin E, vitamin A, carotenoids, BAT – by PUFA,especially n-3 PUFA, bile acids, BeAT – by amino acidrestriction, capsaicin, bile acids, n-3 PUFA, retinoicacid [27]. Low protein diet results in activationof brown adipose tissue, as well as sucrose intakeincrease BAT activity. Some of the diet-derivedsmall molecules shown to increase BAT activityand browning of WAT, such as acetic, butyric andsuccinic acids, ketone bodies. Consumption of chillipeppers (capsaicin, non-pungent capsinoids), oliveoil (oleic acid), green tea (catechins), raspberry(RB-ketone), grapes (resveratrol), fish (PUFAs)also stimulate BAT activation and browning [66].Cannon and Nedergaard described the mechanismof transformation controlled by hypothalamus [67].In the experiment on obese ob/ob mice consumedcafeteria diet (overfed) an activation of brown fat wasobserved – diet-induced thermogenesis (DIT) [33]. Ingeneral, macronutrient content of meals (carbohydrate,fat, protein amount and type) and dietary bioactivecompounds (capsaicin and capsinoids; tea, caffeineand catechins; menthol; conjugated linoleic acid,casein protein, curcumin, garlic powder, procyanidinrichextracts from black soybean seed, resveratrol andextracts from ginger family plants, etc.) could affectBAT and browning process [68]. Interestingly, that14Chernukha I.M. et al. Foods and Raw Materials, 2022, vol. 10, no. 1, pp. 10–18gut microbiota could contribute to upregulation ofthermogenesis in the cold environment [69]. Zhang et al.reported that Caulis spatholobi can activate brownadipose tissue and modulate the composition of gutmicrobiota, which is linked with normalization ofthermogenesis during cooling [70].Most of the research describe functions and roleof WAT, BAT and BeAT in human body. Not manyscientists deal with adipogenic features of white,beige and brown adipose tissues in other mammalian,domestic farm animals in particular.Adipose tissues types in pigs. Database searchsciencedirect.com showed that according to thekeywords “brown fat, white fat”, the system issues3475 publications for 2020, the number of publicationshas doubled in 10 years. 6557 scientific papers werepublished in 2020 for the keywords “brown fat,browning”. When the keyword “pig” is added to thesekeywords, the number of publications is reduced to 356.The analysis of these publications showed that the mainscientific interest is directed on modification of fattyacid composition, but not on the study of the fat typesand their distribution, although the directed modificationof fatty acid profile is of considerable interest, takinginto account correlation of the fatty acids amount withlong chain activity of mitochondrial uncoupling protein1 (UCP1), the activation of the mitochondria of brownfat and non-shivering thermogenesis.Uncoupling protein 1 (UCP1), is a uniquemitochondrial membranous protein devoted to adaptivethermogenesis, a specialized function performedby brown adipocytes [38]. The restricted interest toBAT and BeAT in pigs is explained that pigs (Suidae)have a predominantly tropical distribution and lostfunctional UCP1 in a genetic event that eliminated exons3–5 ~20 million years ago [71–73]. They consequentlyhave also been suggested to lack functional BAT,which is a major cause of neonatal death in the swineindustry [71]. Despite these inconsistent findings, somepig breeds, such as the Tibetan pig found on the Qinghai-Tibetan plateau and the Min pig living in NortheastChina, are well recognized to be cold resistant, andWAT browning was induced after cold exposure as wellas UCP3 expression was significantly increased. Coldresistantpig breeds (eight dominant pig breeds foundacross China) have evolved a novel mechanism involvingUCP3 in beige adipocytes as the primary thermogenicmechanism, challenging the orthodoxy based on studiesof mice that only UCP1 may act as a significant sourceof thermogenic heat [71]. Pigs do not have BAT, butbeige adipocytes were found in inguinal subcutaneousWAT, axillary sWAT and perirenal fat from acute coldstimulatedcold-tolerant pig breeds in China, includingTibetan pigs and Min pigs (Fig. 3) [74]. Differentiatedbeige cells were also observed in subcutaneous fat ofTibetan pigs [71].As beige adipocytes were observed at least in coldstimulated adipose tissues from cold-resistant pigs,UCP1-independent non-shivering thermoregulationmight be justified with temperature maintenance in pigsor UCP3-dependent thermogenesis in beige adipocytesas a key evolutionary response in cold-adapted piglineages [71, 74]. The studies in this area are important,especially concerning neonatal death in the swineindustry and expanding the geography of pig farming.CONCLUSIONWhite, brown and beige/brite adipose tissues areconsidered mainly from the point of view of humanhealth, paying special attention to their role in obesityand type II diabetes. Mechanisms and tools of whiteadipose tissue browning are intensively studied, as wellas brown and beige/brite adipose tissues localizationand features in different species. The phenotypic andgenotypic study of various breeds of pigs in differentconditions of housing, taking into account climaticzones, will reveal the main qualitative characteristicsof fat. The new knowledge about beige adipose tissuewith some similarity to brown, which is characteristicof the neonatal period and almost disappears in theadult body and has a thermogenic function, opens upnew opportunities for the formation of qualitativelynew characteristics of pig adipose tissue. Using theknowledge about the influence of a number of endo- andexogenous factors on the formation of adipose tissue(white, beige, brown), it will be possible to control themolecular mechanisms of adipocyte differentiation inorder to obtain not only high-quality pork fat, but alsomeat products, and to expand the geography of pigbreeding.CONTRIBUTIONThe authors were equally involved in writing themanuscript and are equally responsible for plagiarism.CONFLICT OF INTERESTThe authors state that there is no conflict of interest.