RESUMO
Chronic consumption of a high-fat diet induces obesity and impairs the ultra-structure of organs and tissues. We examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor-dapagliflozin on renal and pancreatic injuries in obese condition. Rats were fed a high-fat diet for 16 weeks to induce obesity. After that, dapagliflozin or vildagliptin, 1.0 or 3.0 mg/kg/day, respectively, was administered by oral gavage for 4 weeks. The effects of dapagliflozin on insulin resistance, kidney autophagy, pancreatic oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and apoptosis in high-fat diet-induced obese rats were elucidated. High-fat-diet fed rats demonstrated metabolic abnormalities including increased body weight, visceral fat weight, plasma insulin, plasma cholesterol, homeostasis model assessment (HOMA) index, and TAUCg, indicating the obese-insulin resistant and glucose intolerance conditions. Also, high-fat-diet fed rats exhibited significant pancreatic injury accompanied by decreased kidney autophagy. Dapagliflozin or vildagliptin treatment for 4 weeks ameliorated pancreatic oxidative stress, ER stress, inflammation, and apoptosis and restored kidney autophagy in obese rats. Moreover, the morphology changes of the pancreas and kidney were improved in the treated groups. Interestingly, dapagliflozin showed higher efficacy than vildagliptin in improving body weight, visceral fat weight, plasma cholesterol level, and pancreatic oxidative stress in our model. Taken together, the present study demonstrated that the therapeutic effects of dapagliflozin attenuated pancreatic injury, pancreatic oxidative stress, ER stress, inflammation, apoptosis, and exerted renoprotective effects by restoring autophagic signaling in obese rats.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Rim/patologia , Obesidade/patologia , Pâncreas/lesões , Pâncreas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Teste de Tolerância a Glucose , Glucosídeos/farmacologia , Inflamação/patologia , Rim/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Vildagliptina/farmacologia , Vildagliptina/uso terapêuticoRESUMO
OBJECTIVE: To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand. METHODS: The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men. RESULTS: The BMD was highest in the age-group 40-49 years and lowest in the age-group 70-87 years. The average T-score at the distal forearm was also highest in the age-group 40-49 years and lowest in the age-group 70-87 years. The BMD decreased as a function of age-group (p < .05). In contrast, the BMD increased as a function of weight (p < .05). Height had weak impact on the BMD in the distal forearm (p > .05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density. CONCLUSIONS: We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.
Assuntos
Densidade Óssea/fisiologia , Antebraço/diagnóstico por imagem , Osteoporose/epidemiologia , Absorciometria de Fóton , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Projetos Piloto , Prevalência , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Tailândia/epidemiologiaRESUMO
(1) Background: Ectopic fat deposition and its effects, metabolic syndrome, have been significantly correlated to lifestyle and caloric consumption. There is no specific noninvasive evaluation tool being used in order to establish clinical markers for tracing the metabolic pathway implicated in obesity-related abnormalities that occur in the body as a result of a high-fat diet (HFD). The purpose of this work is to investigate in vivo ectopic fat distribution and in vitro metabolite profiles given by HFDs, as well as how they are inter-related, in order to find surrogate metabolic biomarkers in the development of metabolic syndrome utilizing noninvasive approaches. (2) Methods: Male Wistar rats were divided into a standard normal chow diet, ND group, and HFD group. After 16 weeks of different diet administration, blood samples were collected for proton nuclear magnetic resonance (1H NMR) and biochemical analysis. Magnetic resonance imaging/proton magnetic resonance spectroscopy (MRI/1H MRS) was performed on the abdomen, liver, and psoas muscle of the rats. (3) Results: Visceral fat showed the strongest relationship with blood cholesterol. Although liver fat content (LFC) was not associated with any biophysical profiles, it had the highest correlation with metabolites such as (-CH2)n very-low-density lipoprotein/low-density lipoprotein (VLDL/LDL), lactate, and N-acetyl glycoprotein of serum 1H NMR. HFD showed no obvious influence on muscle fat accumulation. Acetoacetate, N-acetyl glycoprotein, lactate, (-CH2)n VLDL/LDL, and valine were the five possible metabolic biomarkers used to differentiate HFD from ND in the present study. (4) Conclusions: Our study has validated the influence of long-term HFD-induced ectopic fat on body metabolism as well as the metabolic profile deterioration both in vivo and in vitro.
RESUMO
Radon is the leading source of lung cancer mortality after smoking in Chiang Mai, Thailand. Finding a source of carcinogens is one of the important measures for preventing the cancer risk for this region. Specific sites at Pa Miang, Doi Saket have the highest incidences of lung cancer and have a combination of factors that influence indoor radon concentration. Our study identified the sources of indoor radon within several houses. The results indicate that geological and topographic characteristics, including active faults and mountain terraces, are the main sources of indoor radon, especially for wooden houses. Besides building materials, the design of the houses, ventilation conditions, and lifestyle choices are all factors influencing indoor radon concentrations and its associated risk. Although radon levels (29-101 Bq m-3) and total indoor annual effective doses (0.9-3.8 mSv year-1) received from all sources at these sites have shown no significant health risk due to radon exposure , this investigation will be useful as a starting point to guide strategies to respond and prevent the risk of lung cancer, especially in Chiang Mai.