Dual add-on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study.

AIM: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. RESULTS: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. CONCLUSIONS: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising due to diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function and calcium regulation. This review summarizes the recent scientific findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

The association of low muscle mass with soluble receptor for advanced glycation end products (sRAGE): The Korean Sarcopenic Obesity Study (KSOS).

BACKGROUND: Advanced glycation end products (AGEs) are accumulated with aging in various tissues of humans. The soluble receptor for AGEs (sRAGE) exerts a protective role against the development of aging-related chronic disorders by neutralizing the action of AGEs. We investigated the implication of sRAGE on low muscle mass in Asian men and women. METHODS: This cross-sectional study included a 390-participant, nondiabetic subcohort recruited within the framework of the Korean Sarcopenic Obesity Study, an ongoing prospective cohort study. Low muscle mass was defined based on the distribution of appendicular skeletal muscle mass divided by body mass index, as proposed by the Foundation for the National Institutes Sarcopenia Project. RESULTS: Serum sRAGE levels were significantly lower in participants with low muscle mass than in participants without low muscle mass (0.76 [0.60-1.00] ng/mL vs 0.87 [0.67-1.15] ng/mL, P = .005). In age- and sex-adjusted correlation analyses, appendicular skeletal muscle mass divided by body mass index was associated with sRAGE (r = 0.109, P = .037). Furthermore, decreased circulating levels of sRAGE are independently associated with low muscle mass (odds ratio = 0.254, P = .002) after adjusting for confounding factors, including insulin resistance and inflammatory markers. CONCLUSIONS: The present study shows that a low circulating level of sRAGE may be an independent risk factor for the presence of low muscle mass.

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study.

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.

The implications of sarcopenia and sarcopenic obesity on cardiometabolic disease.

The important changes in body composition associated with aging are a decline in skeletal muscle mass and an increase in body fat. Body fat distribution also changes with age; subcutaneous fat decreases and visceral abdominal fat increase, which contributes to numerous cardiometabolic diseases (CMDs) such as type 2 diabetes, dyslipidemia, and cardiovascular disease (CVD). Sarcopenia often accompanied by an increase in body fat and vice versa, a scenario termed sarcopenic obesity (SO), which might lead to the cumulative risk of both sarcopenia and obesity. However, there is still no consensus regarding the definition and consequences of SO. The lack of a unified definition for SO might contribute to inconsistent findings about the association of SO with CMD. Complex etiologies are associated with development of SO. A vicious cycle between the loss of muscle and the accumulation of ectopic fat might be associated with CMD via an intricate interplay of factors including proinflammatory cytokines, oxidative stress, mitochondrial dysfunction, insulin resistance, dietary energy, physical activity, mitochondrial dysfunction, and other factors that have yet to be identified. Moreover, recent epidemiological studies suggest that SO is related to CVD and mortality. This review focuses on the current literature with regard to the association between sarcopenia, dynapenia, and obesity, as well as their implications for CMD. The ultimate goal of this Prospects is to encourage conduct of well-designed future studies that elucidate the relationship among sarcopenia, SO, and CMD.

Obesity, metabolic abnormality, and knee osteoarthritis: a cross-sectional study in Korean women.

BACKGROUND: This study aimed to analyze the association between knee osteoarthritis and four body size phenotypes defined by the presence or absence of metabolic abnormality and obesity. MEHODS: This was a cross-sectional study using data from 1,549 female participants of the Fifth Korean National Health and Nutrition Examination Survey. Knee osteoarthritis was defined as a Kellgren-Lawrence grade of ≥ 2. Metabolically abnormal state was defined as presence of more than one abnormality among five metabolic risk factors. Obesity was defined using body mass index. Participants were grouped into one of the four body size phenotypes: metabolically healthy normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy obesity (MHO), and metabolically abnormal obesity (MAO). RESULTS: The distribution of each body size phenotype was as follows: MHNW 54.7%, MANW 30.7%, MHO 4.3%, and MAO 10.3%. Prevalence of symptomatic knee osteoarthritis was higher in MANW than in MHNW, and in MAO than in MHO. In multivariable analysis, the association between symptomatic knee osteoarthritis and the body size phenotypes was as follows (OR [95% CI]): MHNW 1.00 (reference), MANW 1.54 (1.15-2.07), MHO 1.61 (0.83-3.13), and MAO 3.47 (2.35-5.14). CONCLUSIONS: Obesity showed closest association with knee osteoarthritis when accompanied by metabolic abnormality.

Knee osteoarthritis is associated with increased prevalence of vertebral fractures despite high systemic bone mineral density: a cross-sectional study in an Asian population.

OBJECTIVES: This study aimed to evaluate the relationship between radiographic knee osteoarthritis and vertebral fractures (VFs) in an Asian population. METHODS: This cross-sectional study involved data from 1,829 participants of the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee osteoarthritis was defined as Kellgren-Lawrence (KL) grades ≥ 2. Prevalent VF was defined as a loss of ≥ 4 cm of height from the peak height. BMD was measured using dual-energy X-ray absorptiometry, in the lumbar spine and femoral neck. RESULTS: In both sexes, the prevalence of VFs increased with age, and was higher in the knee osteoarthritis group than in the control group (in men 13.2 % in osteoarthritis group and 7.9 % in control group; in women 27.7 % in osteoarthritis group and 14.7 % in control group). Age-adjusted BMD at the lumbar spine and femoral neck was significantly higher in the knee osteoarthritis group. In multivariable analysis, KL grade 4 was significantly associated with vertebral fractures in men. In women, there was a significant trend for a positive association between KL grades and vertebral fractures. CONCLUSIONS: Despite high systemic BMD, knee osteoarthritis was positively associated with VFs. These results suggest that bone quality, and consequently bone strength, may be decreased at the systemic level in knee osteoarthritis.

A phase 4 randomized active-controlled clinical study to compare the efficacy and safety of sustained-release pregabalin with immediate-release pregabalin in type 2 diabetic patients with peripheral neuropathic pain.

AIMS: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance. METHODS: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups. RESULTS: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm. CONCLUSIONS: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05624853.

Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean Sarcopenic Obesity Study.

OBJECTIVE: It has been suggested that insulin resistance, low-grade inflammation and vitamin D deficiency are associated with obesity and sarcopenia. However, their relationships with sarcopenic obesity (SO) are unclear. We evaluated the impact of homoeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D (25[OH]D) levels on SO in Korean adults. STUDY SUBJECT/MEASUREMENTS: This study included 493 apparently healthy adults (180 men and 313 women) enrolled in the Korean Sarcopenic Obesity Study. Sarcopenia was defined as a skeletal muscle mass index (SMI) of 1 SD below the sex-specific mean value for a young reference group. Obesity was defined as a visceral fat area (VFA) ≥100 cm(2) . We classified the participants into four sarcopenia/obesity groups based on both SMI and VFA. RESULTS: The prevalence of SO was 17·8% in men and 24·9% in women. In women, the SO group had higher HOMA-IR and hsCRP levels compared with the non-SO group. In men, the 25[OH]D levels were significantly lower in the SO group than the non-SO group. Both hsCRP and HOMA-IR levels were negatively correlated with SMI and positively correlated with VFA in both men and women, whereas 25[OH]D levels were positively correlated with SMI in both men and women. Multiple binary logistic regression analysis showed that HOMA-IR and 25[OH]D levels were independently associated with SO in men, while HOMA-IR and hsCRP were significant factors predicting SO in women. CONCLUSION: Insulin resistance, inflammation and vitamin D deficiency were associated with SO in a Korean adult population.

Sarcopenic obesity is more closely associated with knee osteoarthritis than is nonsarcopenic obesity: a cross-sectional study.

OBJECTIVE: Sarcopenic obesity is a body composition category in which obesity is accompanied by low skeletal muscle mass, offsetting the increase in body weight caused by increased adipose tissue. The purpose of this study was to analyze the association between knee osteoarthritis (OA) and 4 different categories of body composition: normal, sarcopenic nonobesity, nonsarcopenic obesity, and sarcopenic obesity. METHODS: This was a cross-sectional study using the data from 2,893 participants in the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee OA was defined as a Kellgren/Lawrence grade of ≥2. Appendicular skeletal muscle mass (ASM) and whole-body fat mass were measured using dual x-ray absorptiometry. Sarcopenia was defined as a skeletal muscle mass index (ASM/body weight [%]) below -2SD of the value in sex-matched young reference groups. Nonsarcopenic obesity was defined as a body mass index (BMI) ≥27.5 kg/m(2) . RESULTS: The prevalence of each body composition category was as follows: 83.5% normal, 4.3% sarcopenic nonobesity, 9.2% nonsarcopenic obesity, and 3.0% sarcopenic obesity. Compared with nonsarcopenic obesity participants, participants with sarcopenic obesity were significantly older, had lower ASM, higher whole-body fat mass, and higher waist circumference. However, there was no significant difference in body weight or BMI. In multivariate analysis, sarcopenic obesity was more closely associated with radiographic knee OA (OR 3.51 [95% confidence interval (95% CI) 2.15-5.75]) than was nonsarcopenic obesity (OR 2.38 [95% CI 1.80-3.15]). Sarcopenic nonobesity showed no significant association with knee OA. CONCLUSION: Sarcopenic obesity was more closely associated with knee OA than was nonsarcopenic obesity, although both groups had equivalent body weight. This finding supports the importance of the systemic metabolic effect of obesity in knee OA.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study.

AIMS: This study evaluated the efficacy and safety of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor, versus dapagliflozin in Korean patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and gemigliptin. METHODS: In this multicenter, double-blind, randomized study, patients with inadequate response to metformin (≥ 1000 mg/day) plus gemigliptin (50 mg/day) were randomized to receive enavogliflozin 0.3 mg/day (n = 134) or dapagliflozin 10 mg/day (n = 136) in addition to the metformin plus gemigliptin therapy. The primary endpoint was change in HbA1c from baseline to week 24. RESULTS: Both treatments significantly reduced HbA1c at week 24 (-0.92% in enavogliflozin group, -0.86% in dapagliflozin group). The enavogliflozin and dapagliflozin groups did not differ in terms of changes in HbA1c (between-group difference: -0.06%, 95% confidence interval [CI]: -0.19, 0.06) and fasting plasma glucose (between-group difference: -3.49 mg/dl [-8.08;1.10]). An increase in urine glucose-creatinine ratio was significantly greater in the enavogliflozin group than in the dapagliflozin group (60.2 g/g versus 43.5 g/g, P < 0.0001). The incidence of treatment-emergent adverse events was similar between the groups (21.64% versus 23.53%). CONCLUSIONS: Enavogliflozin, added to metformin plus gemigliptin, was well tolerated and as effective as dapagliflozin in the treatment of patients with T2DM.

The differential relationship between fat mass and bone mineral density by gender and menopausal status.

Osteoporosis and obesity are important public health problems in an aging society. We investigated the differential impacts of fat on bone mineral density (BMD) according to gender and menopausal status. We analyzed the baseline data of an ongoing observational cohort study, including a total of 502 healthy subjects 20-88 years of age (144 men, 159 premenopausal women, 199 postmenopausal women). Body composition and fat mass were measured using computed tomography and dual energy X-ray absorptiometry (DXA). BMD was measured at lumbar spines using DXA. In men and postmenopausal women, there was no significant correlation between fat and bone parameters after adjusting for age and body weight. However, in premenopausal women, BMD had significant negative correlations with waist circumference, total fat area, subcutaneous fat area, appendicular fat mass and percentage fat mass after adjusting for age and body weight. Furthermore, only in premenopausal women, the subjects with the highest quartile of percentage fat mass had the lowest BMD even after adjusting for confounding factors including age, body weight, physical activity, alcohol use and smoking history. Multiple linear regression analysis showed that percentage fat mass was a significant negative decisive factor for BMD in premenopausal women. Our study showed the differential relationship between fat mass and BMD according to gender and menopausal status. Only in premenopausal women did fat mass have a significant negative effect on bone mass. This result suggests the importance of reducing fat mass in order to achieve peak bone mass in young adult women.

Type 2 Diabetes Remission with Significant Weight Loss: Definition and Evidence-Based Interventions.

Type 2 diabetes (T2D) has long been regarded as an incurable and chronic disease according to conventional management methods. Clinical and pathophysiological studies on the natural course of T2D have shown that blood glucose control worsens with an increase in the number of required anti-hyperglycemic agents, as ß-cell function progressively declines over time. However, recent studies have shown remission of T2D after metabolic surgery, intensive lifestyle modification, or medications, raising the possibility that ß-cell function may be preserved or the decline in ß-cell function may even be reversible. The World Health Organization as well as the American Diabetes Association and the European Association for the Study of Diabetes recognize remission as an appropriate management aim. In the light of the state of evidence for T2D reversal, physicians need to be educated on treatment options to achieve T2D remission so that they can actively play a part in counseling patients who may wish to explore these approaches to their disease. This review will introduce each of these approaches, summarizing their beneficial effects, supporting evidence, degree of sustainability, and challenges to be addressed in the future.

Prevalence of alcoholic liver disease among Korean adults: results from the fourth Korea National Health and Nutrition Examination Survey, 2009.

BACKGROUND/AIM: Alcohol consumption continues to be a common cause of acute and chronic liver disease. METHODS: Data from a representative sample of 7,893 adults in the Korean National Health and Nutrition Examination Survey 2009 were analyzed. Alcoholic liver disease (ALD) was defined through heavy alcohol consumption (≥40 g/day for men or ≥20 g/day for women) and through elevated liver tests. RESULTS: Approximately 6.7% (95% confidence interval [CI], 6.0-7.4) was at heavy alcohol consumption. Of these "heavy alcohol consumers", one quarter also had ALD. The prevalence of ALD was 1.7% (95% CI, 1.3-2.1). CONCLUSION: ALD is still a burden in the Korean population.

Hepatokines as a Molecular Transducer of Exercise.

Exercise has health benefits and prevents a range of chronic diseases caused by physiological and biological changes in the whole body. Generally, the metabolic regulation of skeletal muscle through exercise is known to have a protective effect on the pathogenesis of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cardiovascular disease (CVD). Besides this, the importance of the liver as an endocrine organ is a hot research topic. Hepatocytes also secrete many hepatokines in response to nutritional conditions and/or physical activity. In particular, certain hepatokines play a major role in the regulation of whole-body metabolic homeostasis. In this review, we summarize the recent research findings on the exercise-mediated regulation of hepatokines, including fibroblast growth factor 21, fetuin-A, angiopoietin-like protein 4, and follistatin. These hepatokines serve as molecular transducers of the metabolic benefits of physical activity in chronic metabolic diseases, including NAFLD, T2D, and CVDs, in various tissues.

Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats.

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagyrelated proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-weekold male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580].