Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Mitsuhiro Okamoto, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
Vol 64 No. 4
Obesity can be associated with systemic low-grade inflammation that leads to obesity-related metabolic disorders. Recent studies raise the possibility that the inflammation in hypothalamus, liver and white adipose tissue (WAT) contributes to the pathogenesis of diet-induced obesity. We focus on the role of interleukin (IL)-10, an anti-inflammatory cytokine produced from spleen in obesity because it is indicated that obesity decreases the expression of pro-inflammatory cytokines in spleen. Obesity results in decrease of IL-10 synthesis from spleen, probably due to reduction of B-cells expression by promoting oxidative stress and apoptosis in spleen. Splenectomy (SPX) aggravates the inflammatory response in hypothalamus, liver and WAT. These SPX-induced alterations are inhibited by systemic administration of IL-10. Moreover, in IL-10 deficiency, SPX had little effect on the inflammatory responses in these multiple organs. We show the role of spleen-derived IL-10 on inflammatory responses in obesity.
Chrishani Rodrigo, Kamani Hemamala Tennekoon, Eric Hamilton Karunanayake, Kanishka De Silva, Indrani Amarasinghe, Ananda Wijayasiri
Vol 64 No. 4
Leptin and visfatin are implicated in breast cancer risk but studies accounting for bioavailability of leptin are sparse. Reports on the association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with breast cancer are also inconsistent. Only a very few studies have examined biochemical and genetic variables concomitantly in the same cohort. A matched pairs study was carried out to ascertain whether plasma leptin, soluble leptin receptor, free leptin index (leptin/soluble leptin receptor), serum visfatin and selected LEP and LEPR polymorphisms are risk factors for sporadic breast cancer. Newly diagnosed sporadic breast cancer patients (N=80) were matched for age, body mass index (BMI) and menopausal status with healthy controls. Plasma leptin, soluble leptin receptor and serum visfatin were measured by enzyme-immunoassay. LEP -2548 A/G and LEPR K109R, LEPR Q223R polymorphisms were determined by genotyping. Leptin (p=0.0234), leptin/BMI (p=0.0468), free leptin index (p<0.0001) and visfatin (p=0.0002) were significantly higher and soluble leptin receptor (p<0.0001) was significantly lower in patients. LEPR gene K109R A/G polymorphism increased breast cancer risk (odds ratio: 4.125). Multivariate analysis confirmed that leptin, soluble leptin receptor, free leptin index and G109 (R109) allele of the LEPR gene K109R polymorphism are risk factors for breast cancer. When stratified by menopausal status free leptin index and soluble leptin receptor remained as risk factors irrespective of menopausal status while LEPR gene K109R A/G polymorphism remained as a risk factor only in the postmenopausal group.
Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial
Ryotaro Bouchi, Yujiro Nakano, Tatsuya Fukuda, Takato Takeuchi, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
Vol 64 No. 3
Liraglutide, an analogue of human glucagon-like peptide 1, reduces cardiovascular events in patients with type 2 diabetes; however, it has still been unknown by which mechanisms liraglutide could reduce cardiovascular events. Type 2 diabetic patients with insulin treatment were enrolled in this randomized, open-label, comparative study. Participants were randomly assigned to liraglutide plus insulin (liraglutide group) and insulin treatment (control group) at 1:1 allocation. Primary endpoint was the change in viscera fat are (VFA, cm2) at 24 weeks. Liver attenuation index (LAI) measured by abdominal computed tomography, urinary albumin-to-creatinine ratio (ACR, mg/g), and C-reactive protein (CRP) levels, skeletal muscle index (SMI), and quality of life (QOL) related to diabetes treatment were also determined. Seventeen patients (8; liraglutide group, 9; control group, mean age 59 ± 13 years; 53% female) completed this study. Liraglutide treatment significantly reduced VFA at 24 weeks; whereas, SFA was unchanged. ACR, LAI, and CRP levels were significantly reduced by liraglutide at 24 weeks and there was no difference in SMI between the two groups. Changes in VFA from baseline to 24 weeks were significantly associated with those in LAI, albuminuria, and HbA1c. Liraglutide treatment significantly improved QOL scores associated with anxiety and dissatisfaction with treatment and satisfaction with treatment. No severe adverse events were observed in both groups. Our data suggest that liraglutide could reduce visceral adiposity in parallel with attenuation of hepatic fat accumulation, albuminuria and micro-inflammation and improve QOL related to diabetes care in insulin-treated patients with type 2 diabetes.
Chih-Chun Chang, Keng-Yang Lin, Kang-Yu Peng, Yuan-Ji Day, Li-Man Hung
Vol 63 No. 2
Studies on resveratrol in a wide range of concentrations on obese mice and adipose cells are necessary to comprehend its range of diverse and contradictory effects. In this study, we examined the anti-obesity effects of resveratrol on high-fat diet (HFD)-induced obese mice at dosages ranging from 1 to 30 mg/kg treatment for 10 wk. We also evaluated the effects of resveratrol on cytotoxicity, proliferation, adipogenic differentiation, and lipolysis of 3T3-L1 cells at concentrations ranging from 0.03 to 100 μM. In HFD obese mice, resveratrol treatment for 10 wk without decreased calories intake significantly attenuated HFD-induced weight gain in a dose-dependent manner. Resveratrol treatment also protected against HFD-induced lipid deposition in adipose tissues and liver. In cultured 3T3-L1 preadipocytes, high dosage (10 to 100 μM) resveratrol treatment produced cytotoxicity in both preadipocytes and mature adipocytes. In contrast, low concentration resveratrol treatment (1 to 10 μM) significantly inhibited the capacity of 3T3-L1 cells differentiated into mature adipocytes. Low dose resveratrol treatment also downregulated peroxisome proliferator-activated receptor gamma (PPARγ) and perilipin protein expressions in differentiated adipocytes. Additionally, tumor necrosis factor alpha (TNFα)-induced lipolysis was inhibited by low concentration resveratrol treatment in mature adipocytes. At concentrations of 10-100 μM, resveratrol exerted cytotoxicity. In contrast, at concentrations of 1-10 μM resveratrol inhibited adipogenic differentiation in preadipocytes and suppressed lipolysis in mature adipocytes. Our results suggest that resveratrol possessed anti-obesity effects by induction of cytotoxicity at high dosage and that it influences preadipocyte differentiation and mature adipocyte lipolysis at low concentration.
Yoshitaka Hashimoto, Takafumi Osaka, Takuya Fukuda, Muhei Tanaka, Masahiro Yamazaki, Michiaki Fukui
Vol 63 No. 10
Recent cross-sectional studies revealed that sarcopenia is associated with non-alcoholic fatty liver disease (NAFLD) in general population. However, it remains to be elucidated that the association between skeletal muscle mass index (SMI) and hepatic steatosis in patients with type 2 diabetes. In this cross-sectional study of 145 Japanese patients (79 men and 66 women) with type 2 diabetes, we examined the correlation of SMI with hepatic steatosis. Skeletal muscle mass was estimated from bioimpedance analysis measurements and SMI (%) was defined as skeletal muscle mass (kg)/total body weight (kg) × 100. Controlled attenuation parameter (CAP) evaluated with transient elastography, was used for assessment of hepatic steatosis. In addition, we also investigated the association between SMI and prevalence of NAFLD, which was defined as CAP over 237.8 dm-1, using logistic regression analysis. Fifty-eight (74%) men and thirty-nine (60%) women had NAFLD. Multiple regression analysis demonstrated that SMI was independently correlated with CAP (β = -0.35, P = 0.007) in men after adjusting for age, body mass index, hemoglobin A1c, triglycerides/ HDL-C ratio, C-reactive protein and gamma-glutamyl transferase. On the other hand, SMI was not associated with CAP in women. Odds ratio per incremental 1% of SMI for prevalence of NAFLD was 0.80 (95% CI 0.64-0.97, P = 0.021) after adjusting for age, BMI, smoking statues, triglycerides/ HDL-C ratio, HbA1c, and gamma-glutamyl transferase in men. In conclusion, SMI was negatively associated with hepatic steatosis in men with type 2 diabetes.
Shinichi Suzuki, Shunichi Yamashita, Toshihiko Fukushima, Keiichi Nakano, Sanae Midorikawa, Akira Ohtsuru, Seiji Yasumura, Mitsunori Hosoya, Kenji Kamiya, Hiroki Shimura, Satoru Suzuki, Izumi Nakamura, Masafumi Abe
Vol 63 No. 3
After the Fukushima nuclear power plant accident on March 11, 2011, the public of Japan became particularly concerned about the possibility of an increased risk of childhood thyroid cancer, similar to what was observed after the Chernobyl’s accident. Due to serious public health perception, there was an urgency to evaluate the baseline levels of childhood thyroid status in Fukushima prefecture. Therefore we have commenced a thyroid ultrasound examination (TUE) survey of the approximately 360,000 pediatric inhabitants (0 to 18 years of age) who lived in Fukushima at the time of the accident in October 2011. The subjects were divided into three categories according to the standardized diagnostic criteria of ultrasound findings. Category A contained the subjects whose TUE findings were intact or benign. Category B were recommended a confirmatory TUE. Category C was recommended an immediate confirmatory TUE. Results: The survey of 40,302 subjects in the first year was completed in March, 2013. There were 40,097 (99.5%), 205 (0.50%) and 0 subjects in categories A, B and C, respectively. Of the 82 category B subjects who underwent fine needle aspiration cytology (FNAC), 12 were diagnosed with a malignant tumor or were suspected to have malignancy. The 12 subjects received thyroid surgery and 11 thyroid cancers and one benign nodule were confirmed histologically after surgery. This is the first large-scaled TUE survey to employ sophisticated ultrasound screening and aim to evaluate the baseline frequency of childhood thyroid nodules and cysts. The results will become the golden standard of future comparative TUE in Fukushima, Japan.
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