Browning Of White Adipocytes Research Articles

Loss of family with sequence similarity 107, member A (FAM107A) induces browning in 3T3-L1 adipocytes

Induction of white fat browning (beiging) and activation of brown fat has been considered a promising strategy to treat obesity and associated metabolic complications. However, the molecular mechanisms regulating brown and beige fat-mediated thermogenesis remains unclear. Our study aimed to identify genes with a hitherto unknown mechanism in the metabolic functions of adipocytes and identified family with sequence similarity 107, member A (FAM107A) as a factor that interferes with fat browning in white adipocytes. We explored physiological roles of FAM107A in cultured 3T3-L1 white adipocytes and HIB1B brown adipocytes by using FAM107A-deficient adipocytes. Significant loss in FAM107A gene functionality induced fat browning was evidenced by evaluating the gene and protein expression level of brown fat-associated markers through real-time qRT-PCR and immunoblot analysis, respectively. Deficiency of FAM107A promoted mitochondrial biogenesis and significantly upregulated core fat-browning marker proteins (PGC-1α, PRDM16, and UCP1) and beige-specific genes (Cd137, Cited1, Tbx1, and Tmem26). Furthermore, FAM107A increased adipogenesis and negatively regulated lipid metabolism in 3T3-L1 adipocytes. In addition, in-silico analysis revealed a strong interaction between FAM107A and β3-AR based on their energy binding score. Next, mechanistic study revealed that specific knockdown of FAM107A induces browning in white adipocytes via activation of β3-AR, AMPK and p38 MAPK-dependent signaling pathways. Our data unveiled a previously unknown mechanism of FAM107A in the regulation of lipid metabolism and identified its significant role in metabolic homeostasis. This highlighted the potential of FAM107A as a pharmacotherapeutic target in treating obesity and related metabolic disorders.

Commentary on: Evidence of Browning of White Adipocytes in Poorly Survived Fat Graft in Patients and Browning of White Adipocytes in Fat Grafts Associated With Higher Level of Necrosis and Type 2 Macrophage Recruitment.

Commentary on: Evidence of Browning of White Adipocytes in Poorly Survived Fat Graft in Patients and Browning of White Adipocytes in Fat Grafts Associated With Higher Level of Necrosis and Type 2 Macrophage Recruitment.

Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). Manf overexpression in liver was also associated with decreased adipose inflammation and improved insulin sensitivity and hepatic steatosis. Mechanistically, Manf could directly promote browning of white adipocytes via the p38 MAPK pathway. Blockade of p38 MAPK abolished Manf-induced browning. Consistently, liver-specific Manf knockout mice showed impaired iWAT browning and exacerbated diet-induced obesity, insulin resistance, and hepatic steatosis. Recombinant Manf reduced obesity and improved insulin resistance in both diet-induced and genetic obese mouse models. Finally, we showed that circulating Manf level was positively correlated with BMI in humans. This study reveals the crucial role of Manf in regulating thermogenesis in adipose tissue, representing a potential therapeutic target for obesity and related metabolic disorders.

Evidence of Browning of White Adipocytes in Poorly Survived Fat Grafts in Patients.

Browning adipocytes induced by burn and cancer were assumed less viable and more prone to necrosis for their hypermetabolic properties. Recent studies have shown browning of white adipose after fat engraftment in mice. The authors sought to evaluate whether fat transfer could induce browning biogenesis in fat grafts in humans and if it is associated with graft necrosis. Necrotic adipose grafts were excised from 11 patients diagnosed with fat necrosis after fat grafting or flap transfer. Non-necrotic fat grafts were from 5 patients who underwent revisionary surgeries after flap transfer. Histology and electronic microscopy as well as protein and gene expression of browning-related marker analyses were performed. Fat grafts with necrosis demonstrated a higher gene expression level of uncoupling protein-1 (greater than fivefold increase, **P < 0.01), a master beige adipocyte marker, than non-necrotic fat grafts. Electronic microscopy and histology showed that browning adipocytes were presented in necrotic adipose in patients. Fat transfer induced browning adipocytes in patients and was evident in patients with postgrafting necrosis.

D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism.

The presence of brown adipocytes within white adipose tissue is associated with phenotypes that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a natural product library comprising 133 compounds with the potential to promote the browning of white adipocytes, and found that D-mannitol induces the browning of 3T3-L1 adipocytes by enhancing the expression of brown fat-specific genes and proteins, and upregulating lipid metabolism markers. D-mannitol also increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 (ACC), suggesting a possible role in lipolysis and fat oxidation. Moreover, an increase in the expression of genes associated with D-mannitol-induced browning was strongly correlated with the activation of the β3-adrenergic receptor as well as AMPK, protein kinase A (PKA), and PPARγ coactivator 1α (PGC1α). D-mannitol effectively reduced the body weight of mice fed a high-fat diet, and increased the expression of β1-oxidation and energy expenditure markers, such as Cidea, carnitine palmityl transferase 1 (CPT1), uncoupling protein 1 (UCP1), PGC1α, and acyl-coenzyme A oxidase (ACOX1) in the inguinal white adipose tissue. Our findings suggest that D-mannitol plays a dual regulatory role by inducing the generation of a brown fat-like phenotype and enhancing lipid metabolism. These results indicate that D-mannitol can function as an anti-obesity supplement.

Browning of White Adipocytes in Fat Grafts Associated With Higher Level of Necrosis and Type 2 Macrophage Recruitment

Induced browning adipocytes were assumed less viable and more prone to necrosis for their hypermetabolic property. A previous study showed that browning of adipocytes was more evident in fat grafts with necrosis in humans. The authors aimed to estimate whether fat transfer-induced browning biogenesis was associated with necrosis and its potential inflammation mechanisms in murine models. Human subcutaneous adipose from thigh or abdomen of 5 patients via liposuction was injected in 100 µL or 500 µL (n = 20 per group) into the dorsal flank of 6- to 8-week-old female nude mice fed with normal chow diet and harvested after 2, 4, 8, and 12 weeks. Control groups did not receive any grafting procedures (sham operation), where lipoaspirates were analyzed immediately after harvest. Histology and electronic microscopy, immunological analyses of browning markers, necrosis marker, and type I/II macrophages markers in mice were performed. Histology and electronic microscopy showed browning adipocytes in fat grafts with a higher level of necrosis (0.435 ± 0.017 pg/mL for cleaved caspase-3, **P < 0.01), IL-6 (749.0 ± 134.1 pg/mL,***P < 0.001) and infiltration of type 2 macrophage profiles in mice (twofold increase, *P < 0.05). Browning of adipocytes induced by fat transfer in mice is in parallel with post-grafting necrotic levels associated with elevated interleukin-6 and activated type 2 macrophage profiles, which promote browning development.

BMP11 regulates thermogenesis in white and brown adipocytes.

Bone morphogenetic protein-11 (BMP11), also known as growth differentiation factor-11 (GDF11), is implicated in skeletal development and joint morphogenesis in mammals. However, its functions in adipogenesis and energy homeostasis are mostly unknown. The present study investigates crucial roles of BMP11 in cultured 3T3-L1 white and HIB1B brown adipocytes, using Bmp11 gene depletion and pharmacological inhibition of BMP11. The silencing of Bmp11 markedly decreases the expression levels of brown-fat signature proteins and beige-specific genes in white adipocytes and significantly down-regulates the expression levels of brown fat-specific genes in brown adipocytes. The deficiency of Bmp11 reduces the expressions of lipolytic protein markers in white and brown adipocytes. Moreover, BMP11 induces browning of 3T3-L1 adipocytes via coordination of multiple signalling pathways, including mTORC1-COX2 and p38MAPK-PGC-1α as non-canonical pathways, as well as Smad1/5/8 as a canonical pathway. We believe this study is the first to provide evidence of the potential roles of BMP11 for improvement of lipid catabolism in both cultured white and brown adipocytes, as well as the effect on browning of white adipocytes. Taken together, these results demonstrate the therapeutic potential for the treatment of obesity.

Cissus Quadrangularis enhances UCP1 mRNA, indicative of white adipocyte browning and decreases central obesity in humans in a randomized trial

Obesity is associated with the growth and expansion of adipocytes which could be decreased via several mechanisms. Cissus Quadrangularis (CQ) extract has been shown to reduce obesity in humans; however, its effect on human white adipocytes (hWA) has not been elucidated. This study aimed to investigate the effects of CQ on obesity, lipolysis, and browning of hWA. CQ treatment in obese humans significantly decreased waist circumference at week 4 and week 8 when compared with the baseline values (p < 0.05 all) and significantly decreased hip circumference at week 8 when compared with the baseline and week 4 values (p < 0.05 all). Serum leptin levels of the CQ-treated group were significantly higher at week 8 compared to baseline levels (p < 0.05). In hWA, glycerol release was reduced in the CQ-treated group when compared with the vehicle-treated group. In the browning experiment, pioglitazone, the PPAR-γ agonist, increased UCP1 mRNA when compared to vehicle (p < 0.01). Interestingly, 10, 100, and 1000 ng/ml CQ extract treatment on hWA significantly enhanced UCP1 expression in a dose-dependent manner when compared to pioglitazone treatment (p < 0.001 all). In conclusion, CQ decreased waist and hip circumferences in obese humans and enhanced UCP1 mRNA in hWA suggestive of its action via browning of hWA.

Epigenetic Regulators of White Adipocyte Browning.

Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT can induce metabolic disorders such as dyslipidemia, obesity, and diabetes. Preadipocytes or adipocytes from WAT possess sufficient plasticity as they can transdifferentiate into brown-like beige adipocytes. Studies in both humans and rodents showed that brown and beige adipocytes could improve metabolic health and protect from metabolic disorders. Brown fat requires activation via exposure to cold or β-adrenergic receptor (β-AR) agonists to protect from hypothermia. Considering the fact that the usage of β-AR agonists is still in question with their associated side effects, selective induction of WAT browning is therapeutically important instead of activating of BAT. Hence, a better understanding of the molecular mechanisms governing white adipocyte browning is vital. At the same time, it is also essential to understand the factors that define white adipocyte identity and inhibit white adipocyte browning. This literature review is a comprehensive and focused update on the epigenetic regulators crucial for differentiation and browning of white adipocytes.

Synergistic Treatment of Obesity via Locally Promoting Beige Adipogenesis and Antioxidative Defense in Adipose Tissues.

Obesity is a primary risk factor for type 2 diabetes, cardiovascular diseases, cancer, and other chronic diseases. Current antiobesity medications need frequent administration and show limited efficacy with severe side effects. Herein, browning agent rosiglitazone (Rsg) and antioxidant manganese tetroxide nanoparticles (MnNPs, around 250 nm) are integrated into electrospun short fibers (SF@Rsg-Mn) with a 1.5 μm width and a 20 μm length. Upon injection into inguinal adipose tissues, SF@Rsg-Mn are well retained in the local depots to sustainably release Rsg in 30 days for adipose tissue browning, while MnNPs on the fiber surface continuously scavenge adipose reactive oxygen species (ROS) for an extended period of time. Synergistic inhibition of fat accumulation through ROS scavenging and white adipocyte browning has been demonstrated for the first time, and the optimal synergistic ratio of Rsg and MnNPs is determined to be 1/14 via combination index examination. SF@Rsg-Mn inhibit lipid accumulation through downregulation of adipogenic gene PPARγ while promoting energy expenditure through upregulation of brown-specific gene UCP1 and mitochondrial function gene COX7A1. In a diet-induced obesity mouse model, a single injection of SF@Rsg-Mn into inguinal adipose tissues has accomplished a synergistic effect on body weight loss, fat reduction, glucose, and lipid metabolic improvement while minimizing adverse effects on other tissues, thereby paving the way to efficacious, safe, and practical treatment of obesity.

Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha

ObjectiveErythropoietin (EPO), the cytokine required for erythropoiesis, contributes to metabolic regulation of fat mass and glycemic control. EPO treatment in mice on high-fat diets (HFD) improved glucose tolerance and decreased body weight gain via reduced fat mass in males and ovariectomized females. The decreased fat accumulation with EPO treatment during HFD in ovariectomized females was abrogated with estradiol supplementation, providing evidence for estrogen-related gender-specific EPO action in metabolic regulation. In this study, we examined the cross-talk between estrogen mediated through estrogen receptor α (ERα) and EPO for the regulation of glucose metabolism and fat mass accumulation. MethodsWild-type (WT) mice and mouse models with ERα knockout (ERα−/−) and targeted deletion of ERα in adipose tissue (ERαadipoKO) were used to examine EPO treatment during high-fat diet feeding and after diet-induced obesity. ResultsERα−/− mice on HFD exhibited increased fat mass and glucose intolerance. EPO treatment on HFD reduced fat accumulation in male WT and ERα−/− mice and female ERα−/− mice but not female WT mice. EPO reduced HFD increase in adipocyte size in WT mice but not in mice with deletion of ERα independent of EPO-stimulated reduction in fat mass. EPO treatment also improved glucose and insulin tolerance significantly greater in female ERα−/− mice and female ERαadipoKO compared with WT controls. Increased metabolic activity by EPO was associated with browning of white adipocytes as shown by reductions in white fat-associated genes and induction of brown fat-specific uncoupling protein 1 (UCP1). ConclusionsThis study clearly identified the role of estrogen signaling in modifying EPO regulation of glucose metabolism and the sex-differential EPO effect on fat mass regulation. Cross-talk between EPO and estrogen was implicated for metabolic homeostasis and regulation of body mass in female mice.

Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and β3-AR activation

Brown adipose tissue (BAT) activation or beige adipocytes in white adipocytes (WAT) (browning) is a novel strategy against obesity. Corylin, a flavonoid compound extract from Psoralea corylifolia L., has been shown to exert anti-inflammatory, anticancer, and anti-atherosclerotic effects and ameliorate hyperlipidemia and insulin resistance. However, the therapeutic effect of corylin on obesity remains unknown. The objective of this study was to evaluate the effect of corylin on browning or obesity. Here, we report that corylin induced browning by elevating the expression levels of beige‐ or browning-specific marker genes, including cited1, hoxc9, pgc1α, prdm16, and ucp1, in 3T3‐L1 adipocytes, WAT and BAT. Moreover, corylin also strikingly reduced body weight and fat accumulation and increased insulin sensitivity, mitochondrial biogenesis, and β-oxidation in HFD- and DIO-treated mice. The browning and lipolysis effects of corylin were abolished by sirtuin 1 (SIRT1) inhibitor (EX527) and β3-adrenergic receptor (β3-AR) antagonist (L-748,337) treatment. The possible molecular mechanism of corylin on the browning and lipolysis of adipocytes is through SIRT1- or β3-AR-dependent pathways. The study suggested that corylin exerts anti-obesity effects through the browning of white adipocytes, activating of BAT and promoting of lipid metabolism. Therefore, corylin may be a helpful therapeutic candidate for treating obesity.

The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes.

Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity. Activation of these receptors induce browning of white adipocyte. The purpose of this work was to characterize the role of carnosic acid (CA), a compound used in traditional medicine, in the control of brown/brite adipocyte formation and function. We used human multipotent adipose-derived stem (hMADS) cells differentiated into white or brite adipocytes. The expression of key marker genes was determined using RT-qPCR and western blotting. We show here that CA inhibits the browning of white adipocytes and favors decreased gene expression of thermogenic markers. CA treatment does not affect β-adrenergic response. Importantly, the effects of CA are fully reversible. We used transactivation assays to show that CA has a PPARα/γ antagonistic action. Our data pinpoint CA as a drug able to control PPAR activity through an antagonistic effect. These observations shed some light on the development of natural PPAR antagonists and their potential effects on thermogenic response.

Role of Inositols and Inositol Phosphates in Energy Metabolism.

Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, they may also have distinctive properties in energy metabolism and metabolic disorders. We review inositols and inositol phosphate metabolism in mammalian cells to establish their biological activities and highlight their potential roles in energy metabolism. These molecules are known to decrease insulin resistance, increase insulin sensitivity, and have diverse properties with importance from cell signaling to metabolism. Evidence showed that inositol phosphates might enhance the browning of white adipocytes and directly improve insulin sensitivity through adipocytes. In addition, inositol pyrophosphates containing high-energy phosphate bonds are considered in increasing cellular energetics. Despite all recent advances, many aspects of the bioactivity of inositol phosphates are still not clear, especially their effects on insulin resistance and alteration of metabolism, so more research is needed.

The Effect of FOXC2-AS1 on White Adipocyte Browning and the Possible Regulatory Mechanism.

Obesity has become a worldwide epidemic, and obesity-related problems are becoming more severe in public health. Increasing brown adipose tissue (BAT) mass or/and activity in mice and humans has been demonstrated to help lose weight and improve whole-body metabolism. Studies on the conversion of white adipose tissue (WAT) to BAT under certain conditions have provided new possibilities for treating obesity and the related disorders. It has been established that long non-coding RNAs (lncRNAs) play an important role in the regulation of mouse adipocyte differentiation and thermogenic programs; however, the function and potential mechanism of lncRNA in the process of human white adipocyte browning remains unclear. In the present study, we identified a lncRNA called Forkhead Box C2 antisense RNA 1 (FOXC2-AS1), which was first identified in osteosarcoma, and it was highly expressed in human adipocytes but decreased during the white adipocyte differentiation program. FOXC2-AS1 expression was also induced by the thermogenic agent forskolin. Lentivirus-mediated overexpression of FOXC2-AS1 in human white adipocytes did not affect lipid drop accumulation, but significantly promoted the browning phenotype, as revealed by the increased respiratory capacity and the enhanced protein expression levels of brown adipocyte-specific markers. In contrast, inhibiting FOXC2-AS1 with small interfering RNA led to attenuated thermogenic capacity in human white adipocytes. RNA-sequencing analysis and western blot were used to identify a possible regulatory role of the autophagy signaling pathway in FOXC2-AS1 to mediate white-to-brown adipocyte conversion. The autophagy inhibitor 3-methyladenine restored the reduced UCP1 protein level and thermogenic capacity caused by inhibiting FOXC2-AS1. Overall, the present study characterized the potential role of FOXC2-AS1 and further identified a lncRNA-mediated mechanism for inducing browning of human white adipocytes and maintaining thermogenesis, further providing a potential strategy for treating obesity and related disorder.

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects.

Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.

Trigonelline induces browning in 3T3-L1 white adipocytes.

Trigonelline, a major alkaloid component of fenugreek, has been demonstrated to have several biological activities, including antidiabetic and anticancer effects. This study aimed to examine the possible application of trigonelline as an anti-obesity compound based on an investigation of its enhancement of lipid catabolism and induction of browning in white adipocytes. Trigonelline induces browning of 3T3-L1 white adipocytes by enhancing the expressions of brown-fat signature proteins and genes as well as beige-specific genes, including Cd137, Cited1, Tbx1, and Tmem26. Trigonelline also improves lipid metabolism in white adipocytes by decreasing adipogenesis and lipogenesis as well as promotes lipolysis and fatty acid oxidation. Moreover, trigonelline increases the expression of Cox4, Nrf1, and Tfam genes that are responsible for mitochondrial biogenesis. Mechanistic studies revealed that the browning effect of trigonelline in 3T3-L1 white adipocytes is mediated by activating β3-AR and inhibiting PDE4, thereby stimulating the p38 MAPK/ATF-2 signaling pathway. Considering its high bioavailability in humans and the results of this study, trigonelline may have potential as an anti-obesity compound.

Browning of White Adipocyte in Poorly Survived Fat Grafts in Mice and Fat Transplantation Patients

Journal of the American College of Surgeons 231(4):p e182, October 2020. | DOI: 10.1016/j.jamcollsurg.2020.08.482

Angiotensin AT1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin

Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT1 receptor) signaling. Here, we report that losartan, a selective AT1 receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT1 receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The in vivo browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, in vivo apelin knockdown by adeno-associated virus carrying-apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT1 receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders.

The myokine irisin: localization and effects in swine late medium and large antral ovarian follicle

Irisin is mainly synthesized by skeletal muscle tissue, where it is believed to be responsible for the benefits of exercise on metabolism and cardiovascular system. In adipose tissue, its best-known effect is the browning of white adipocytes, resulting in the increase of thermogenesis and energy expenditure. As it has been largely documented that metabolic dysfunctions can frequently be associated with reductions in fertility, the possible involvement of this molecule in the regulation of reproductive processes represents an issue to be addressed. On this basis, the first aim of this work was the evaluation of the presence of irisin in the swine ovary; then, we investigated the expression of the associated molecules FNDC5, PGC-1α, and PPAR-γ. To verify a potential modulatory role both on ovarian function and on redox status, cell growth, steroidogenesis, production of superoxide anion and nitric oxide, the nonenzymatic antioxidant scavengers, were assessed in vitro on granulosa cells treated with increasing concentrations of irisin (50, 100, and 150 ng/mL). The data collected demonstrate the presence of irisin in swine ovarian follicle. Moreover, the highest concentrations tested stimulated metabolic activity and inhibited cell proliferation (P < 0.05); the peptide exerted a biphasic effect on progesterone (P < 0.01) production and, at the highest concentrations, inhibited nitric oxide while stimulated the nonenzymatic antioxidant power (P < 0.05). Superoxide anion and estradiol 17β were unaffected. The demonstration of the local presence of irisin at the ovarian level and the highlighted effects allow us to qualify this molecule as a potential physiological regulator of follicular function.