Brown Adipocyte Differentiation Research Articles

Albizia julibrissin Exerts Anti-Obesity Effects by Inducing the Browning of 3T3L1 White Adipocytes.

This study investigated the effects of the Albizia julibrissin Leaf extracts (AJLE) on adipocytes using 3T3-L1 cells. AJLE inhibited adipogenesis by reducing the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding proteins (C/EBPs) that regulate enzymes involved in fat synthesis and storage, and subsequently reduced intracellular lipid droplets, glycerol-3-phosphate dehydrogenase (GPDH), and triglyceride (TG). AJLE also increased the expression of brown adipocyte markers, such as uncoupling protein-1 (UCP-1), PR/SET domain 16 (PRDM16), and bone morphogenetic protein 7 (BMP7) by inducing the differentiation of brown adipocytes, as shown by a decrease in the lipid droplet sizes and increasing mitochondrial mass. AJLE increased the expression of transcription factor A, mitochondrial (TFAM), mitochondrial DNA (mtDNA) copy number, and UCP-1 protein expression, all of which are key factors in regulating mitochondrial biogenesis. AJLE-induced browning was shown to be regulated by the coordination of AMPK, p38, and SIRT1 signaling pathways. The ability of AJLE to inhibit adipogenesis and induce brown adipocyte differentiation may help treat obesity and related diseases.

Mitochondrial respiratory complex I deficiency inhibits brown adipogenesis by limiting heme regulation of histone demethylation

Mitochondrial functions play a crucial role in determining the metabolic and thermogenic status of brown adipocytes. Increasing evidence reveals that the mitochondrial oxidative phosphorylation (OXPHOS) system plays an important role in brown adipogenesis, but the mechanistic insights are limited. Herein, we explored the potential metabolic mechanisms leading to OXPHOS regulation of brown adipogenesis in pharmacological and genetic models of mitochondrial respiratory complex I deficiency. OXPHOS deficiency inhibits brown adipogenesis through disruption of the brown adipogenic transcription circuit without affecting ATP levels. Neither blockage of calcium signaling nor antioxidant treatment can rescue the suppressed brown adipogenesis. Metabolomics analysis revealed a decrease in levels of tricarboxylic acid cycle intermediates and heme. Heme supplementation specifically enhances respiratory complex I activity without affecting complex II and partially reverses the inhibited brown adipogenesis by OXPHOS deficiency. Moreover, the regulation of brown adipogenesis by the OXPHOS-heme axis may be due to the suppressed histone methylation status by increasing histone demethylation. In summary, our findings identified a heme-sensing retrograde signaling pathway that connects mitochondrial OXPHOS to the regulation of brown adipocyte differentiation and metabolic functions.

Transcriptomic Analysis Reveals Fibroblast Growth Factor 11 (FGF11) Role in Brown Adipocytes in Thermogenic Regulation of Goats.

Brown adipose tissue (BAT) is the main site of adaptive thermogenesis, generates heat to maintain body temperature upon cold exposure, and protects against obesity by promoting energy expenditure. RNA-seq analysis revealed that FGF11 is enriched in BAT. However, the functions and regulatory mechanisms of FGF11 in BAT thermogenesis are still limited. In this study, we found that FGF11 was significantly enriched in goat BAT compared with white adipose tissue (WAT). Gain- and loss-of-function experiments revealed that FGF11 promoted differentiation and thermogenesis in brown adipocytes. However, FGF11 had no effect on white adipocyte differentiation. Furthermore, FGF11 promoted the expression of the UCP1 protein and an EBF2 element was responsible for UCP1 promoter activity. Additionally, FGF11 induced UCP1 gene expression through promoting EBF2 binding to the UCP1 promoter. These results revealed that FGF11 promotes differentiation and thermogenesis in brown adipocytes but not in white adipocytes of goats. These findings provide evidence for FGF11 and transcription factor regulatory functions in controlling brown adipose thermogenesis of goats.

Miquelianin, a main functional flavonoid of lotus leaf, induces thermogenic signature via p38‐PINK1‐PARKIN‐mediated mitophagy and mimicking NRF2 signaling during brown adipocyte differentiation

AbstractAdipocytes thermogenesis is an important mechanism for increasing energy expenditure. Here, screening of thermogenic activators (Sirt1 and Ucp1) investigated in C3H10T1/2 cells revealed ethanol extract of lotus leaf (LLE) may exert higher activity compared with that of the other 11 ingredients. UPLC‐MS/MS analysis showed that miquelianin was identified as the main flavonoid compounds in LLE (12.8%) and therefore deserves further investigation. The results in C3H10T1/2 cells revealed miquelianin promoted lipolysis, enhanced thermogenic programming (Sirt1, Ppargc1a, Prdm16, Cox7a, Nrf1, Cox2, and Ucp1), and induced brown‐like adipocyte formation (Fgf21, Cd137, Tmem26, Tbx1, Cd40, and Cited1). Moreover, miquelianin increased mitochondrial abundance, mitochondrial membrane potential, and NAD+/NADH ratio, suggesting its potential in mitochondria activity. We also observed that miquelianin improved mitochondrial quality by the establishment of mitochondrial dynamics (Mfn1, Mfn2, Opa1, Drp1, and Fis1) and subsequent suppression of autophagy. Chemical inhibition experiment revealed miquelianin may trigger browning via p38‐PINK1‐PARKIN‐mediated mitophagy. Furthermore, in ML385‐treated cells, NRF2, HMOX1, TFAM, and UCP1 were compromised by miquelianin treatment, suggesting that NRF2 signaling is necessary during miquelianin‐induced mitochondria biogenesis. Together, our findings demonstrate that miquelianin may induce browning and mitochondria thermogenic programing by suppressing mitophagy via p38‐PINK1‐PARKIN and mimicking NRF2 signaling.

LncDGAT2 is a novel positive regulator of the goat adipocyte thermogenic gene program

Brown and beige adipose thermogenesis are important for newborn mammals to maintain their body temperature. In addition, these thermogenic fats are regulated by multiple molecular interactions. How the long non-coding RNAs (lncRNAs) regulate adipose thermogenesis in newborn mammals upon cold exposure remains unexplored. Here, we identified lncRNAs induced by cold exposure in brown adipose tissue (BAT) of newborn goats and found that lncDGAT2 was enriched in BAT after cold exposure. Functional studies revealed that lncDGAT2 promoted brown and white adipocyte differentiation as well as thermogenic gene expression. Additionally, PRDM4 directly bound the lncDGAT2 promoter to activate the transcription of lncDGAT2 and the PRDM4-lncDGAT2 axis was essential for the brown adipocyte thermogenic gene program. These findings provide evidence for lncRNA and transcription factor regulatory functions in controlling adipose thermogenesis and energy metabolism of newborn goats.

Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity.

The angiotensin II type 2 receptor (AT2R) exerts vasorelaxant, anti-inflammatory, and antioxidant properties. In obesity, its activation counterbalances the adverse cardiovascular effects of angiotensin II mediated by the AT1R. Preliminary results indicate that it also promotes brown adipocyte differentiation in vitro. Our hypothesis is that AT2R activation could increase BAT mass and activity in obesity. Five-week-old male C57BL/6J mice were fed a standard or a high-fat (HF) diet for 6 weeks. Half of the animals were treated with compound 21 (C21), a selective AT2R agonist, (1 mg/kg/day) in the drinking water. Electron transport chain (ETC), oxidative phosphorylation, and UCP1 proteins were measured in the interscapular BAT (iBAT) and thoracic perivascular adipose tissue (tPVAT) as well as inflammatory and oxidative parameters. Differentiation and oxygen consumption rate (OCR) in the presence of C21 was tested in brown preadipocytes. In vitro, C21-differentiated brown adipocytes showed an AT2R-dependent increase of differentiation markers (Ucp1, Cidea, Pparg) and increased basal and H+ leak-linked OCR. In vivo, HF-C21 mice showed increased iBAT mass compared to HF animals. Both their iBAT and tPVAT showed higher protein levels of the ETC protein complexes and UCP1, together with a reduction of inflammatory and oxidative markers. The activation of the AT2R increases BAT mass, mitochondrial activity, and reduces markers of tissue inflammation and oxidative stress in obesity. Therefore, insulin reduction and better vascular responses are achieved. Thus, the activation of the protective arm of the renin-angiotensin system arises as a promising tool in the treatment of obesity.

Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator.

The in vitro study of white, brown, and beige adipocyte differentiation enables the investigation of cell-autonomous functions of adipocytes and their mechanisms. Immortalized white preadipocyte cell lines are publicly available and widely used. However, the emergence of beige adipocytes in white adipose tissue in response to external cues is difficult to recapitulate to the full extent using publicly available white adipocyte cell lines. Isolation of the stromal vascular fraction (SVF) from murine adipose tissue is commonly executed to obtain primary preadipocytes and perform adipocyte differentiation. However, mincing and collagenase digestion of adipose tissue by hand can result in experimental variation and is prone to contamination. Here, we present a modified semi-automated protocol that utilizes a tissue dissociator for collagenase digestion to achieve easier isolation of the SVF, with the aim of reducing experimental variation, reducing contamination, and increasing reproducibility. The obtained preadipocytes and differentiated adipocytes can be used for functional and mechanistic analyses.

Optical diffraction tomography and Raman spectroscopy reveal distinct cellular phenotypes during white and brown adipocyte differentiation

White adipose tissue (WAT) and brown adipose tissue (BAT) are the primary types of fats in humans, and they play prominent roles in energy storage and thermogenesis, respectively. While the mechanisms of terminal adipogenesis are well understood, much remains unknown about the early stages of adipogenic differentiation. Label-free approaches, such as optical diffraction tomography (ODT) and Raman spectroscopy, offer the ability to retrieve morphological and molecular information at the single cell level without the negative effects of photobleaching and system perturbation due to introduction of fluorophores. In this study, we employed 3D ODT and Raman spectroscopy to gain deeper insights into the early stages of differentiation of human white preadipocytes (HWPs) and human brown preadipocytes (HBPs). We utilized ODT to retrieve morphological information, including cell dry mass and lipid mass, and Raman spectroscopy to obtain molecular information about lipids. Our findings reveal that HWPs and HBPs undergo dynamic and differential changes during the differentiation process. Notably, we found that HBPs accumulated lipids more rapidly and had a higher lipid mass than HWPs. Additionally, both cell types experienced an increase and subsequent decrease in cell dry mass during the first seven days, followed by an increase after day 7, which we attribute to the transformation of adipogenic precursors in the early stages. Finally, HBPs had higher lipid unsaturation levels than HWPs for the same differentiation timepoints. The insights gained from our study provide crucial contributions towards the advancement of new therapies for obesity and related diseases.

Adipose tissue plasticity in pheochromocytoma patients suggests a role of the splicing machinery in human adipose browning

Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype.

The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.

Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function. We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function. We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST. In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.

A Novel LncRNA MSTRG.310246.1 Promotes Differentiation and Thermogenesis in Goat Brown Adipocytes.

Brown adipose tissue (BAT) plays a critical role in maintaining the body temperature in newborn lamb due to its unique non-shivering thermogenesis. Previous studies have found that BAT thermogenesis is regulated by several long non-coding RNAs (lncRNAs). Here, we identified a novel lncRNA, MSTRG.310246.1, which was enriched in BAT. MSTRG.310246.1 was localized in both the nuclear and cytoplasmic compartments. In addition, MSTRG.310246.1 expression was upregulated during brown adipocyte differentiation. Overexpression of MSTRG.310246.1 increased the differentiation and thermogenesis of goat brown adipocytes. On the contrary, the knockdown of MSTRG.310246.1 inhibited the differentiation and thermogenesis of goat brown adipocytes. However, MSTRG.310246.1 had no effect on goat white adipocyte differentiation and thermogenesis. Our results show that MSTRG.310246.1 is a BAT-enriched LncRNA that improves the differentiation and thermogenesis of goat brown adipocytes.

Mevalonate biosynthesis pathway regulates the development and survival of brown adipocytes

The high thermogenic activity of brown adipose tissue (BAT) has received considerable attention. Here, we demonstrated the role of the mevalonate (MVA) biosynthesis pathway in the regulation of brown adipocyte development and survival. The inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme in the MVA pathway and the molecular target of statins, suppressed brown adipocyte differentiation by suppressing protein geranylgeranylation-mediated mitotic clonal expansion. The development of BAT in neonatal mice exposed to statins during the fetal period was severely impaired. Moreover, statin-induced geranylgeranyl pyrophosphate (GGPP) deficiency led to the apoptosis of mature brown adipocytes. Brown adipocyte-specific Hmgcr knockout induced BAT atrophy and disrupted thermogenesis. Importantly, both genetic and pharmacological inhibition of HMGCR in adult mice induced morphological changes in BAT accompanied by an increase in apoptosis, and statin-treated diabetic mice showed worsened hyperglycemia. These findings revealed that MVA pathway-generated GGPP is indispensable for BAT development and survival.

COBL, MKX and MYOC Are Potential Regulators of Brown Adipose Tissue Development Associated with Obesity-Related Metabolic Dysfunction in Children

Obesity is already accompanied by adipose tissue (AT) dysfunction and metabolic disease in children and increases the risk of premature death. Due to its energy-dissipating function, brown AT (BAT) has been discussed as being protective against obesity and related metabolic dysfunction. To analyze the molecular processes associated with BAT development, we investigated genome-wide expression profiles in brown and white subcutaneous and perirenal AT samples of children. We identified 39 upregulated and 26 downregulated genes in uncoupling protein 1 (UCP1)-positive compared to UCP1-negative AT samples. We prioritized for genes that had not been characterized regarding a role in BAT biology before and selected cordon-bleu WH2 repeat protein (COBL), mohawk homeobox (MKX) and myocilin (MYOC) for further functional characterization. The siRNA-mediated knockdown of Cobl and Mkx during brown adipocyte differentiation in vitro resulted in decreased Ucp1 expression, while the inhibition of Myoc led to increased Ucp1 expression. Furthermore, COBL, MKX and MYOC expression in the subcutaneous AT of children is related to obesity and parameters of AT dysfunction and metabolic disease, such as adipocyte size, leptin levels and HOMA-IR. In conclusion, we identify COBL, MKX and MYOC as potential regulators of BAT development and show an association of these genes with early metabolic dysfunction in children.

Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice.

Brown adipose tissue (BAT) is only present in mammals and has a thermogenic function. Brown adipocytes are characterized by a multilocular cytoplasm with multiple lipid droplets, a central nucleus, a high mitochondrial content, and the expression of uncoupling protein 1 (UCP1). BAT has been proposed as a potential therapeutic target for obesity and its associated metabolic disorders due to its ability to dissipate metabolic energy as heat. To investigate BAT function and regulation, brown adipocyte culturing is indispensable. The present protocol optimizes tissue processing and cell differentiation for culturing brown adipocytes from newborn mice. Additionally, procedures for the imaging of differentiated adipocytes with both confocal immunofluorescence and transmission electron microscopy are shown. In the brown adipocytes differentiated with the techniques described herein, the major defining features of classical BAT are preserved, including high UCP1 levels, increased mitochondrial mass, and very close physical contact between the lipid droplets and mitochondria, making this method a valuable tool for BAT studies.

Bidirectional effect of vitamin D on brown adipogenesis of C3H10T1/2 fibroblast-like cells.

Brown adipose tissue (BAT) dissipates caloric energy as heat and plays a role in glucose and lipid metabolism. Therefore, augmentation and activation of BAT are the focus of new treatment strategies against obesity, a primary risk factor of metabolic syndrome. The vitamin D system plays a crucial role in mineral homeostasis, bone metabolism, and cell proliferation and differentiation. In this study, we investigated the effects of vitamin D3 [1,25(OH)2D3] on brown adipocyte differentiation. The mouse fibroblast-like cell line C3H10T1/2 was differentiated into brown adipocytes in the presence of 1,25(OH)2D3. The effect of 1,25(OH)2D3 on brown adipocyte differentiation was assessed by measuring lipid accumulation, the expression of related genes, and cytotoxicity. The viability of C3H10T1/2 cells was measured using the Cell Counting Kit-8 assay. Gene expression was investigated using quantitative reverse transcription-polymerase chain reaction. Protein expression was estimated using western blotting. 1,25(OH)2D3 inhibited adipocyte differentiation and exerted a cytotoxic effect at 1 nM. However, in the physiological concentration range (50-250 pM), 1,25(OH)2D3 promoted uncoupling protein 1 (UCP1) expression in C3H10T1/2 cells. This effect was not observed when 1,25(OH)2D3 was added 48 h after the initiation of differentiation, suggesting that the vitamin D system acts in the early phase of the differentiation program. We showed that 1,25(OH)2D3 increased the expression of two key regulators of brown adipogenesis, PR domain containing 16 (Prdm16) and peroxisome proliferator-activated receptor γ coactivator-1α (Pgc1α ). Furthermore, 1,25(OH)2D3 increased Ucp1 expression in 3T3-L1 beige adipogenesis in a dose-dependent manner. These data indicate the potential of vitamin D and its analogs as therapeutics for the treatment of obesity and related metabolic diseases.

Myoglobin-mediated lipid shuttling increases adrenergic activation of brown and white adipocyte metabolism and is as a marker of thermogenic adipocytes in humans.

Recruitment and activation of brown adipose tissue (BAT) results in increased energy expenditure (EE) via thermogenesis and represents an intriguing therapeutic approach to combat obesity and treat associated diseases. Thermogenesis requires an increased and efficient supply of energy substrates and oxygen to the BAT. The hemoprotein myoglobin (MB) is primarily expressed in heart and skeletal muscle fibres, where it facilitates oxygen storage and flux to the mitochondria during exercise. In the last years, further contributions of MB have been assigned to the scavenging of reactive oxygen species (ROS), the regulation of cellular nitric oxide (NO) levels and also lipid binding. There is a substantial expression of MB in BAT, which is induced during brown adipocyte differentiation and BAT activation. This suggests MB as a previously unrecognized player in BAT contributing to thermogenesis. This study analyzed the consequences of MB expression in BAT on mitochondrial function and thermogenesis in vitro and in vivo. Using MB overexpressing, knockdown or knockout adipocytes, we show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, signalling and lipolysis. Overexpression in white adipocytes also increases their metabolic activity. Mutation of lipid interacting residues in MB abolished these beneficial effects of MB. In vivo, whole-body MB knockout resulted in impaired thermoregulation and cold- as well as drug-induced BAT activation in mice. In humans, MB is differentially expressed in subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots, differentially regulated by the state of obesity and higher expressed in AT samples that exhibit higher thermogenic potential. These data demonstrate for the first time a functional relevance of MBs lipid binding properties and establish MB as an important regulatory element of thermogenic capacity in brown and likely beige adipocytes.

Breathe and burn: Novel roles for myoglobin in thermogenesis

Breathe and burn: Novel roles for myoglobin in thermogenesis

Circular RNA circZEB1 regulates goat brown adipocytes differentiation and thermogenesis through miR-326–3p

Circular RNA (circRNA) is involved in various biological processes. However, the regulatory roles of circRNA on brown adipose tissue (BAT) thermogenesis still remain to be elucidated. In this study, we characterized circZEB1, which was enriched in BAT and derived from exon 2 and exon 3 of goat ZEB1 gene. Sanger sequencing and RNase R assay demonstrated that circZEB1 was a head-to-tail structure with a length of 298 bp. Besides, the expression levels of circZEB1 were upregulated during brown adipocytes differentiation and circZEB1 was mainly located in cytoplasm. Furthermore, circZEB1 promoted brown adipocytes differentiation and thermogenesis. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay indicated that circZEB1 could bind to miR-326–3p in brown adipocytes. In addition, miR-326–3p reduced the lipid accumulation of brown adipocytes, whereas overexpression of circZEB1 reversed the inhibition effects of miR-326–3p on lipid deposition. The results demonstrated that circZEB1 regulated brown adipocytes differentiation and thermogenesis through circZEB1/miR-326–3p pathway.

MiR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis.

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to promote white adipocyte differentiation, its role in BAT remains unclear. In our study, we found that during HFD-induced obesity, the expression of miR-143 in BAT was significantly reduced, and the expression of miR-143 in WAT first increased and then decreased. Knockout (KO) of miR-143 with CRISPR/Cas9 did not affect the energy metabolism of normal diet fed mice and brown adipocyte differentiation but inhibited the differentiation of white adipocytes. Importantly, during high fat diet-induced obesity, miR-143KO significantly reduced body weight, and improved energy expenditure, insulin sensitivity, and glucose tolerance. Further exploration showed that miR-143KO reduced the weight of adipose tissue, promoted mitochondrial number and functions, induced thermogenesis and lipolysis of BAT, increased lipolysis, and inhibited lipogenesis of white adipose tissue (WAT). Our study considerably improves our collective understanding of the function of miR-143 in adipose tissue and its potential significance in anti-obesity and provides a new avenue for the management of obesity through the inhibition of miR-143 in BAT and WAT.

Porphyromonas gingivalis‑derived lipopolysaccharide inhibits brown adipocyte differentiation via lncRNA‑BATE10.

Epidemiological studies have suggested an association between obesity and periodontal disease. Brown adipose tissue (BAT) has an anti-obesity effect. However, the effects of periodontitis on obesity and BAT remain unclear. Therefore, the present study aimed to determine the effects of lipopolysaccharide derived from Porphyromonas gingivalis (P. gingivalis LPS) on brown adipocytes. For this purpose, the present study examined the effects of the intravenous administration of Porphyromonas gingivalis (P. gingivalis) in mice, the treatment of brown adipocytes with P. gingivalis LPS during differentiation, and the administration of small interfering RNA targeting interferon on brown preadipocytes by assessing the expression of genes involved in differentiation, using a long non-coding (lnc)RNA, and pro-inflammatory factors using reverse transcription-quantitative PCR. In addition, the accumulation of lipid droplets was examined using Oil Red O staining. P. gingivalis LPS reduced the expression of uncoupling protein 1 (UCP1) and lncRNA-BATE10 in brown adipocytes during differentiation. Consistent with this finding, P. gingivalis reduced UCP1 and lncRNA-BATE10 expression in the BAT of mice. lncRNA-BATE10 may thus be involved in the regulation of UCP1 expression that occurs during the differentiation of brown adipocytes treated with P. gingivalis LPS. Thus, P. gingivalis LPS may inhibit BAT differentiation by reducing lncRNA-BATE10 expression.