Irisin Expression Research Articles

Exercise in the heat induces similar elevations in serum irisin in young and older men despite lower resting irisin concentrations in older adults.

Irisin is thought to play a cytoprotective role during acute stressors, such as exercise, by reducing oxidative stress and inflammation. Relative to young adults, older individuals exhibit an impaired capacity to dissipate heat during exercise, which can exacerbate elevations in oxidative stress and the acute inflammatory response especially in the heat. In turn, this could induce a greater increase in circulating irisin. Thus, we evaluated age-related differences in irisin expression during prolonged exercise in a non-heat stress and high-heat stress environment. Specifically, we assessed serum irisin in 12 young (22±3 years) and 12 older (59±4 years) men before and after 3-h moderate-intensity exercise (metabolic rate: 200W/m2) and 60-min post-exercise recovery in temperate (wet-bulb globe temperature (WBGT) 16°C) and hot (WBGT 32°C) environments. Core temperature (Tco) was measured continuously. Post-exercise Tco was similarly higher in the hot compared to the temperate condition for both groups (p<0.001), although Tco remained elevated at end-recovery in the heat in older but not young adults (p=0.006). Absolute serum irisin concentrations were significantly higher (p≤0.002) under all conditions in the young relative to older adults. Post-exercise and end-recovery irisin was elevated above baseline in both groups in the hot (+39.3pg/mL SEM 8 and+48.9pg/mL SEM 10, respectively; both p≤0.043) but not the temperate condition. When comparing between conditions, the change in irisin concentrations at post-exercise did not differ, although serum irisin was elevated in the hot (+48.9pg/mL SEM 10) relative to the temperate (+0.88pg/mL SEM 0.2) condition in both groups at end-recovery (p=0.004). Our findings indicate that irisin concentrations were elevated after exercise compared to rest in hot, but not temperate conditions across groups. However, older adults may still have greater cellular vulnerability to heat stress given their blunted circulating irisin levels.

HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia.

Exposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Our results showed that 4 w of hypoxia exposure significantly reduced body weight and gastrocnemius muscle mass of mice, as well as grip strength and the duration time of treadmill exercise. Hypoxic treatment increased HIF-1α expression and decreased both the circulation level of irisin and its precursor protein FNDC5 expression in skeletal muscle. In in vitro, CoCl2-induced chemical hypoxia and 1% O2 ambient hypoxia both reduced FNDC5, along with the increase in HIF-1α. Moreover, the decline in the area and diameter of myotubes caused by hypoxia were rescued by inhibiting HIF-1α via YC-1. Collectively, our research indicated that FNDC5/irisin was negatively regulated by HIF-1α and could participate in the regulation of muscle atrophy caused by hypoxia.

Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice.

BackgroundChronic renal failure induces bone mineral disorders and sarcopenia. Skeletal muscle affects other tissues, including bone, by releasing myokines. However, the effects of chronic renal failure on the interactions between muscle and bone remain unclear.MethodsWe investigated the effects of renal failure on bone, muscle, and myokines linking muscle to bone using a mouse 5/6 nephrectomy (Nx) model. Muscle mass and bone mineral density (BMD) were analysed by quantitative computed tomography 8 weeks after Nx.ResultsNephrectomy significantly reduced muscle mass in the whole body (12.1% reduction, P < 0.05), grip strength (10.1% reduction, P < 0.05), and cortical BMD at the femurs of mice (9.5% reduction, P < 0.01) 8 weeks after surgery, but did not affect trabecular BMD at the femurs. Among the myokines linking muscle to bone, Nx reduced the expression of irisin, a proteolytic product of fibronectin type III domain‐containing 5 (Fndc5), in the gastrocnemius muscles of mice (38% reduction, P < 0.01). Nx increased myostatin mRNA levels in the gastrocnemius muscles of mice (54% increase, P < 0.01). In simple regression analyses, cortical BMD, but not trabecular BMD, at the femurs was positively related to Fndc5 mRNA levels in the gastrocnemius muscles of mice (r = 0.651, P < 0.05). The weekly administration of recombinant irisin to mice ameliorated the decrease in cortical BMD, but not muscle mass or grip strength, induced by Nx (6.2% reduction in mice with Nx vs. 3.3% reduction in mice with Nx and irisin treatment, P < 0.05).ConclusionsThe present results demonstrated that renal failure decreases the expression of irisin in the gastrocnemius muscles of mice. Irisin may contribute to cortical bone loss induced by renal failure in mice as a myokine linking muscle to bone.

Beta-glucan: A powerful antioxidant to overcome cyclophosphamide-induced cardiotoxicity in rats

Cyclophosphamide (CP) is a common chemotherapeutic drug; however, it does have several toxic side effects, including cardiotoxicity. Beta (β)-glucan is a free radical scavenger and powerful antioxidative molecule. The effects of β-glucan on CP-induced cardiotoxicity were investigated in this experimental study. Twenty-eight Wistar albino rats were divided into the following four equal groups: control (no treatment), CP (200 mg/kg CP, intraperitoneally on day 2), β-glucan (50 mg/kg β-glucan, oral gavage for seven days), and CP+β-glucan (200 mg/kg CP, intraperitoneally on day 2+50 mg/kg β-glucan, oral gavage for seven days) groups. Histopathology, irisin, and caspase-3 expressions were evaluated in ventricular myocardial tissues. The CP group exhibited considerably more severe cardiac damage than the control group, according to histological evaluation. Immunohistochemically irisin expression was decreased, and caspase-3 expression was much higher in the CP group. β-glucan, on the other hand, improved histopathological changes and exhibited a protective potential against CP-induced cardiac tissue damage when combined with the CP group. Our findings showed that β-glucan could act as an effective cardioprotective molecule against the toxic effects caused by CP.

Significance of Irisin (FNDC5) Expression in Colorectal Cancer.

The role of irisin, the extracellular part of fibronectin type III domain containing 5 (FNDC5), in colorectal cancer (CRC) is unclear. The aim of this study was to investigate immunohistochemical (IHC) expression level of irisin and correlations with clinicopathological factors in patients with CRC. We collected 222 archived CRC samples and 26 control samples from autopsies conducted at the Department of Forensic Medicine. They were used to perform IHC reactions detecting irisin, Ki-67, minichromosome maintenance protein complex component 3 (MCM3), and urine diphosphate-galactose ceramide galactosyltransferase (UGT3) expression. The correlations with Ki-67, MCM3, and UGT3 were analyzed. Irisin expression was also evaluated in cancer cell lines by immunofluorescence reaction and western blot. Irisin expression was higher in cancer cells compared to the control tissues (p<0.0001). Irisin expression was significantly higher in stage I than in stage III (p=0.013) and IV CRC (p=0.05). The correlation between higher expression of irisin and cancer stages indicates its potential usefulness as a marker in CRC.

Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx.

Background: Current studies indicate irisin role in carcinogenesis. The aim of the study was to investigate the expression of irisin in LSCCs and to determine its association with clinicopathological factors, as well as recognized markers of proliferation, i.e., Ki-67 and MCM3,5,7 and MT-I/II proteins. Material and methods: The research material consisted of 140 cases of LSCCs, 57 cases of laryngeal papillomas (BLs) and 14 controls (benign hypertrophic changes). Tissue microarrays were used to perform IHC. Western blot and immunofluorescence were performed in laryngeal cancer cell lines and normal keratinocytes. Results: Irisin expression levels were significantly increased in LSCC compared to BLs (p < 0.0001) and controls (p = 0.001). We noted a positive moderate and weak correlation between irisin and Ki-67, MCM3 and MT-I/II. We observed an elevated level of irisin expression with increasing tumor size (T1–2 vs. T3–4; p = 0.0348). The levels of irisin were higher in N0 than in N1 and N2–3 (p = 0.0031 and p = 0.0457, respectively). Our in vitro study revealed a higher level of irisin in Larynx Epidermoid Carcinoma 2 (HEp-2) cells compared to the control Normal Human Keratinocyte (HaCat) cell line. Conclusions: Increased irisin expression levels in LSCC and its correlation with clinicopathological and proliferation factors may indicate the potential role of irisin as a biomarker in the diagnostic process of LSCC.

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2.

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.

Vitellogenin 2 promotes muscle development and stimulates the browning of white fat.

Eggs are rich in nutrients and contain a lot of protein. Although eggs have proved to accelerate the growth of C2C12 cells, the regulatory and mechanism of fertilized egg yolk extract (FEYE) on skeletal muscle development and fat metabolism remains unclearly. The mice were treated with FEYE by gavage for 24 d, we found that FEYE can inhibit the expression of skeletal muscle atrophy genes such as MSTN and Murf-1, and up-regulate the expression levels of MYOD, MYOG and Irisin. In addition, the treatment of FEYE induced UCP1 and PGC1α high expression in WAT, thereby causing WAT browning reaction. In order to confirm the composition of FEYE, we performed protein full spectrum identification (LC MS/MS) analysis and found the most enriched component is vitellogenin 2 (VTG2). Therefore, we added the recombinant protein VTG2 to C2C12 cells and found that VTG2 promoted the proliferation and differentiation of C2C12 cells. After that, we further proved that VTG2 inhibited the expression of MSTN and improved the expression of MYOD and Irisin. Finally, the dual luciferase test proved that VTG2 directly inhibited the transcriptional activity of MSTN. Our results conclude that FEYE inhibits the expression of MSTN in muscle tissues by delivering VTG2, thereby promoting skeletal muscle development, and can also promote the expression level of FNDC5 in serum. Then, FNDC5 acts on the fat through the serum, stimulating the browning reaction of white adipocytes. Therefore, VTG2 can be used to stop muscle consumption, improve skeletal muscle aging, and prevent obesity.

Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis.

To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.

Irisin levels in the serum and cerebrospinal fluid of patients with multiple sclerosis and the expression and distribution of irisin in experimental autoimmune encephalomyelitis.

Irisin is a novel hormone-like myokine that plays an important role in central nervous system (CNS) diseases, such as cerebral ischaemia and Alzheimer's disease. However, irisin is rarely investigated in multiple sclerosis (MS), a typical inflammatory demyelinating disease of the CNS, and in experimental autoimmune encephalomyelitis (EAE), a typical model of MS. We determined the levels of irisin in the serum and cerebrospinal fluid in patients with MS. The expression and histological distribution of irisin were determined in EAE. Serum irisin levels in patients with MS and in EAE mice were increased, and the levels of FNDC5/irisin mRNA were decreased in the spinal cord and brain regardless of the onset, peak or chronic phase of EAE. Immunofluorescence staining showed co-localization of irisin and neurones. The levels of irisin fluctuated with disease progression in MS and EAE. Irisin may be involved in the pathological process of MS/EAE.

Increased FNDC5/IRISIN protein expression in breast cancer tissue is associated with obesity in postmenopausal women

AimTo analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates...

Effect of high-intensity interval training on fat reduction and irisin expression in obese rats

Effect of high-intensity interval training on fat reduction and irisin expression in obese rats

Ameliorative effects of garlic oil on FNDC5 and irisin sensitivity in liver of streptozotocin-induced diabetic rats.

This study was aimed to investigate the effects of garlic oil (GO), an important natural constituent used in alleviating diabetes and its complications, on the expression levels of irisin and related genes. Thirty-two rats were divided into four groups: Control, Diabetes-Control, Diabetes+GO 100 mg/kg/day and Control+GO 100 mg/kg/day for 45 days. The measurements included: changes in liver Peroxisome proliferator-activated receptor-gamma-coactivator (PGC)-1α, Fibronectin Type-III-Domain-Containing5 (FNDC5), irisin expression, mRNA expression of p38 and TNF-α (Tumour necrosis factor-α), total-antioxidant-status (L-TAS; S-TAS), total-oxidant-status (L-TOS; S-TOS) in liver and serum, respectively. There was a significant reduction in serum levels of irisin and S-TAS and expression of PGC-1α and FNDC5 in liver in Diabetes-control compared to Control-group, while a significant increase in serum levels of fasting blood glucose (FBG) and TOS, also p38 and TNF-α expressions in liver. In Diabetes+GO group, there was a significant increase in serum irisin and S-TAS, also expression of PGC-1α and FNDC5 in liver, while serum FBG, S-TOS levels, and mRNA expression of p38 and TNF-α in liver were decreased compared to Diabetes-control group (P < 0.05). GO alleviated the diabetic liver injury by decreasing Oxidative-Stress parameters and regulation PGC-lα, FNDC5, irisin and P38, keeping the balance of TAS/TOS and TNF-α.

FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-α pathway.

Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high‐fat diet (HFD). Increases in muscle atrophy markers (FOXO‐3, Atrogin‐1, MuRF‐1) were abrogated by FGF19 in palmitic acid (PA)‐treated C2C12 myotubes and in the skeletal muscle of HFD‐fed mice. FGF19 not only reduced HFD‐induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC‐1α, UCP‐1, PPAR‐γ) in brown adipose tissue (BAT). FGF19 treatment restored PA‐ and HFD‐induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS‐1, GLUT‐4) and mitigated the PA‐ and HFD‐induced decrease in FNDC‐5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT‐1 and PGC‐1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity‐induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT‐1/PGC‐α signalling pathway, which might be a potential therapeutic target for obesity and SO.

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin.

ObjectiveRecent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats.MethodsThe middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke.ResultsCompared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (p<0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (p>0.05).ConclusionEA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.

Role of irisin in effects of chronic exercise on muscle and bone in ovariectomized mice.

Exercise is beneficial for the prevention and treatment of osteoporosis. Skeletal muscle affects other tissues via myokines, the release of which is regulated by acute exercise. However, the effects of chronic exercise on myokines linking muscle to bone have not been fully elucidated. Therefore, we investigated the effects of chronic exercise on bone and myokines using ovariectomized (OVX) mice. Treadmill exercise with moderate intensity was performed for 8weeks after OVX or sham surgery. We measured bone mineral density (BMD) at the femurs and tibias of mice by quantitative computed tomography and myokine mRNA levels in the gastrocnemius and soleus muscles. Treadmill exercise ameliorated decreases in trabecular and cortical BMD in the femurs of OVX mice. Irisin is a proteolytic product of fibronectin type III domain-containing 5 (Fndc5). Among the myokines examined, treadmill exercise increased irisin protein and Fndc5 mRNA levels in the gastrocnemius and soleus muscles of sham and OVX mice. Treadmill exercise increased peroxisome proliferator-activated receptor γ coactivator-1α mRNA levels in the gastrocnemius muscles of mice. Fndc5 mRNA levels in the gastrocnemius muscles positively correlated with trabecular BMD, but not with cortical BMD, at the femurs and tibias of mice in simple regression analyses. We demonstrated that chronic exercise elevated irisin expression in the gastrocnemius and soleus muscles of estrogen-deficient mice. Irisin might be related to increases in trabecular BMD in mice; however, further studies are needed to clarify the involvement of irisin in the effects of chronic exercise on muscle/bone interactions.

Myokines in treatment-naïve patients with cancer-associated cachexia

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N=62), or not (weight stable cancer, WSC, N=32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p=0.047), higher FABP3 plasma content (p=0.0301) and higher tumor tissue expression of FABP3 (p=0.0182), IL-15 (p=0.007) and irisin (p=0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p=0.0149, p=0.0455 and p=0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p=0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

抗肥満効果をもつirisin のビタミンA による発現制御

抗肥満効果をもつirisin のビタミンA による発現制御

Irisin Gene Delivery Ameliorates Burn-Induced Sensory and Motor Neuropathy.

Burn-related neuropathy is common and often involves pain, paresthesia, or muscle weakness. Irisin, an exercise-induced myokine after cleavage from its membrane precursor fibronectin type III domain-containing 5 (FNDC5), exhibits neuroprotective and anti-inflammatory activities. A rat model of third-degree burn on the right hind paw was used to investigate the therapeutic role of irisin/FNDC5. Rats received burn injury and were treated with intrathecal recombinant adenovirus containing the irisin sequence (Ad-irisin) at 3 weeks postburn. One week later, mechanical allodynia was examined. The expression of irisin in cerebrospinal fluid (CSF) was detected. Ipsilateral gastrocnemius muscle and lumbar spinal cord were also obtained for further investigation. Furthermore, the anti-apoptotic effect of recombinant irisin in SH-SY5Y cells was evaluated through tumor necrosis factor alpha (TNFα) stimulus to mimic burn injury. We noted intrathecal Ad-irisin attenuated pain sensitization and gastrocnemius muscle atrophy by modulating the level of irisin in CSF, and the expression of neuronal FNDC5/irisin and TNFα in the spinal cord. Ad-irisin also ameliorated neuronal apoptosis in both dorsal and ventral horns. Furthermore, recombinant irisin attenuated TNFα-induced SH-SY5Y cell apoptosis. In summary, irisin attenuated allodynia and muscle wasting by ameliorating neuroinflammation-induced neuronal apoptosis.

β-hydroxy-β-methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue.

The effects of resistance training (RT) associated with calcium β-hydroxyβ-methylbutyrate (CaHMB) supplementation on the body composition and gene expression of cytokines related to skeletal muscle hypertrophy and adipose tissue metabolism were studied in rats. Male Wistar rats were divided into four groups of 12 animals: sedentary control (SC); sedentary supplemented (SS); resistance training control (RTC) and resistance training supplemented (RTS). Rats from RTC and RTS groups were submitted to an RT programme and those from SS and RTS groups received 1 mL of CaHMB (320 mg kg-1 day-1) by gavage, for 8 weeks. We evaluated: body composition; plasma lipid profile; the gene expression of interleukin (IL)-6, IL-10, IL-15 and fibronectin type III domain-containing protein 5 (FNDC-5) in skeletal muscle, and IL-6, mitochondrial uncoupling protein 1 (UCP-1) in white adipose tissue (WAT); and the concentration of irisin in WAT. Compared to RTC alone, the combination of CaHMB with RT (RTS) further reduced abdominal circumference (5.3%), Lee index (2.4%), fat percentage (24.4%), plasma VLDL cholesterol (16.8%) and triglycerides (17%) and increased the gene expression of FNDC-5 (78.9%) and IL-6 (47.4%) in skeletal muscle and irisin concentration (26.9%) in WAT. Neither RT nor CaHMB affected the protein percentage or the gene expression of IL-6 and UCP-1 in WAT and IL-10, IL-15 in skeletal muscle. In conclusion, CaHMB supplementation increased the beneficial effects of RT on body fat reduction and was associated with muscular genic expression of IL-6 and FNDC-5 and irisin concentration in WAT, despite the lack of change in protein mass and maximal strength.