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1.
Nat Commun ; 15(1): 2102, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453901

RESUMO

Nicotinamide adenine dinucleotide (NAD)+ serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed salvage pathway. Here we show that treatment with saturated fatty acids activates the NAD+ salvage pathway in hypothalamic astrocytes. Furthermore, inhibition of this pathway mitigates hypothalamic inflammation and attenuates the development of obesity in male mice fed a high-fat diet (HFD). Mechanistically, CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. The activation of the astrocytic NAMPT-NAD+-CD38 axis in response to fat overload induces proinflammatory responses in the hypothalamus. It also leads to aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes. Our findings highlight the significant contribution of the hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, to HFD-induced obesity.


Assuntos
Gorduras na Dieta , NAD , Masculino , Camundongos , Animais , NAD/metabolismo , Gorduras na Dieta/metabolismo , Astrócitos/metabolismo , Obesidade/metabolismo , Hipotálamo/metabolismo , Citocinas/metabolismo
2.
Diabetes Metab J ; 47(5): 575-594, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37793979

RESUMO

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.


Assuntos
Dislipidemias , Estado Pré-Diabético , Adulto , Humanos , Povo Asiático , República da Coreia/epidemiologia , Sociedades Médicas , Diabetes Mellitus
3.
Endocrinol Metab (Seoul) ; 38(6): 597-618, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37828708

RESUMO

Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Aldosterona , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/terapia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , República da Coreia/epidemiologia
4.
Endocrinol Metab (Seoul) ; 38(2): 245-252, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016490

RESUMO

BACKGRUOUND: Coronavirus disease 2019 (COVID-19) can cause various extrapulmonary sequelae, including diabetes. However, it is unclear whether these effects persist 30 days after diagnosis. Hence, we investigated the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in the post-acute phase of COVID-19. METHODS: This cohort study used data from the Health Insurance Review and Assessment Service, a representative national healthcare database in Korea. We established a cohort of 348,180 individuals diagnosed with COVID-19 without a history of diabetes between January 2020 and September 2021. The control group consisted of sex- and age-matched individuals with neither a history of diabetes nor COVID-19. We assessed the hazard ratios (HR) of newly diagnosed T2DM patients with COVID-19 compared to controls, adjusted for age, sex, and the presence of hypertension and dyslipidemia. RESULTS: In the post-acute phase, patients with COVID-19 had an increased risk of newly diagnosed T2DM compared to those without COVID-19 (adjusted HR, 1.30; 95% confidence interval [CI], 1.27 to 1.33). The adjusted HRs of non-hospitalized, hospitalized, and intensive care unit-admitted patients were 1.14 (95% CI, 1.08 to 1.19), 1.34 (95% CI, 1.30 to 1.38), and 1.78 (95% CI, 1.59 to 1.99), respectively. The risk of T2DM in patients who were not administered glucocorticoids also increased (adjusted HR, 1.29; 95% CI, 1.25 to 1.32). CONCLUSION: COVID-19 may increase the risk of developing T2DM beyond the acute period. The higher the severity of COVID-19 in the acute phase, the higher the risk of newly diagnosed T2DM. Therefore, T2DM should be included as a component of managing long-term COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , COVID-19/epidemiologia , COVID-19/complicações , Incidência , República da Coreia/epidemiologia
5.
Diabetes Metab J ; 47(2): 201-210, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36750233

RESUMO

BACKGROUND: We evaluated the validity and reliability of the operational definition of type 2 diabetes mellitus (T2DM) based on the Korean National Health Insurance Service (NHIS) database. METHODS: Adult subjects (≥40 years old) included in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2017 were merged with those from the NHIS health check-up database, producing a cross-sectional dataset. We evaluated the sensitivity, specificity, accuracy, and agreement of the NHIS criteria for defining T2DM by comparing them with the KNHANES criteria as a standard reference. RESULTS: In the study population (n=13,006), two algorithms were devised to determine from the NHIS dataset whether the diagnostic claim codes for T2DM were accompanied by prescription codes for anti-diabetic drugs (algorithm 1) or not (algorithm 2). Using these algorithms, the prevalence of T2DM was 14.9% (n=1,942; algorithm 1) and 20.8% (n=2,707; algorithm 2). Good reliability in defining T2DM was observed for both algorithms (Kappa index, 0.73 [algorithm 1], 0.63 [algorithm 2]). However, the accuracy (0.93 vs. 0.89) and specificity (0.96 vs. 0.90) tended to be higher for algorithm 1 than for algorithm 2. The validity (accuracy, ranging from 0.91 to 0.95) and reliability (Kappa index, ranging from 0.68 to 0.78) of defining T2DM by NHIS criteria were independent of age, sex, socioeconomic status, and accompanied hypertension or dyslipidemia. CONCLUSION: The operational definition of T2DM based on population-based NHIS claims data, including diagnostic codes and prescription codes, could be a valid tool to identify individuals with T2DM in the Korean population.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Inquéritos Nutricionais , Reprodutibilidade dos Testes , Programas Nacionais de Saúde , República da Coreia/epidemiologia
6.
Korean J Intern Med ; 37(6): 1099-1110, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36300322

RESUMO

Musculoskeletal conditions are common in patients with diabetes. Several musculoskeletal disorders are viewed as chronic complications of diabetes because epidemiological studies have revealed high correlations between such complications and diabetes, but the pathophysiological links with diabetes remains unclear. Genetic predispositions, shared risk factors, microvascular impairments, progressive accumulation of advanced glycation end-products, and diabetic neuropathy may underlie the development of musculoskeletal disorders. Musculoskeletal complications of diabetics have received less attention than life-threatening microvascular or macrovascular complications. Here, we review several diabetic musculoskeletal complications with a focus on the clinical importance of early recognition and management, which would improve quality of life and physical function.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Doenças Musculoesqueléticas , Humanos , Qualidade de Vida , Diabetes Mellitus/epidemiologia , Complicações do Diabetes/etiologia , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/etiologia , Fatores de Risco
7.
J Obes Metab Syndr ; 31(2): 100-122, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35670159

RESUMO

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

8.
Diabetes Metab J ; 46(3): 377-390, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35656561

RESUMO

The Joint Committee of the Korean Diabetes Association, the Korean Society for the Study of Obesity, and the Korean Society of Hypertension announced a consensus statement on carbohydrate-restricted diets and intermittent fasting, representing an emerging and popular dietary pattern. In this statement, we recommend moderately-low-carbohydrate or low-carbohydrate diets, not a very-low-carbohydrate diet, for patients with type 2 diabetes mellitus. These diets can be considered a dietary regimen to improve glycemic control and reduce body weight in adults with type 2 diabetes mellitus. This review provides the detailed results of a meta-analysis and systematic literature review on the potential harms and benefits of carbohydrate-restricted diets in patients with diabetes. We expect that this review will help experts and patients by fostering an in-depth understanding and appropriate application of carbohydrate-restricted diets in the comprehensive management of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Adulto , Dieta com Restrição de Carboidratos , Humanos , Obesidade , República da Coreia/epidemiologia
9.
Diabetes Metab J ; 46(3): 355-376, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35656560

RESUMO

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Adulto , Dieta com Restrição de Carboidratos , Jejum , Humanos , Obesidade , Sobrepeso , República da Coreia
10.
Diabetes Metab J ; 46(3): 417-426, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35656565

RESUMO

BACKGROUND: This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults. METHODS: We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018. RESULTS: Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c) <6.5% was 24.5% despite the increased use of new antidiabetic medications. We found that adults with diabetes mellitus who achieved all three goals of HbA1c <6.5%, blood pressure (BP) <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL were 9.7%. The percentage of self-management behaviors was lower in men than women. Excess energy intake was observed in 16.7% of adults with diabetes mellitus. CONCLUSION: The prevalence of diabetes mellitus among Korean adults remained high. Only 9.7% of adults with diabetes mellitus achieved all glycemic, BP, and lipid controls from 2019 to 2020. Continuous evaluation of national diabetes statistics and a national effort to increase awareness of diabetes mellitus and improve comprehensive diabetes care are needed.


Assuntos
Diabetes Mellitus , Adulto , Estudos Transversais , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Inquéritos Nutricionais , República da Coreia/epidemiologia
11.
Diabetes Metab J ; 46(5): 701-712, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35654585

RESUMO

BACKGROUND: To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims. RESULTS: Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF. CONCLUSION: The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dipeptidil Peptidases e Tripeptidil Peptidases , Feminino , Glucose , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Hipoglicemiantes , Prescrições , República da Coreia/epidemiologia , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
12.
Clin Hypertens ; 28(1): 26, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642007

RESUMO

BACKGROUND: Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. METHODS: A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled clinical trials (RCTs) of carbohydrate-restricted diets and ten articles on eight RCTs of IF was performed. RESULTS: Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. CONCLUSION: Here, we describe the results of our analysis and the evidence for these recommendations.

13.
Endocrinol Metab (Seoul) ; 37(1): 9-25, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35255598

RESUMO

Evidence for involvement of the central nervous system (CNS) in the regulation of glucose metabolism dates back to the 19th century, although the majority of the research on glucose metabolism has focused on the peripheral metabolic organs. Due to recent advances in neuroscience, it has now become clear that the CNS is indeed vital for maintaining glucose homeostasis. To achieve normoglycemia, specific populations of neurons and glia in the hypothalamus sense changes in the blood concentrations of glucose and of glucoregulatory hormones such as insulin, leptin, glucagon-like peptide 1, and glucagon. This information is integrated and transmitted to other areas of the brain where it eventually modulates various processes in glucose metabolism (i.e., hepatic glucose production, glucose uptake in the brown adipose tissue and skeletal muscle, pancreatic insulin and glucagon secretion, renal glucose reabsorption, etc.). Errors in these processes lead to hyper- or hypoglycemia. We here review the current understanding of the brain regulation of glucose metabolism.


Assuntos
Glucagon , Insulina , Sistema Nervoso Central/metabolismo , Glucagon/metabolismo , Glucose , Homeostase/fisiologia , Insulina/metabolismo
14.
World J Clin Cases ; 9(33): 10198-10207, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34904090

RESUMO

BACKGROUND: Neuropathy is a common chronic complication in type 2 diabetes mellitus (T2DM). Statin and metformin are commonly used medications in T2DM patients, and some studies showed statin- or metformin-induced neuropathy. AIM: To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies. METHODS: Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used. Patients with T2DM and no complications were divided into statin/metformin/statin + metformin users and non-users. Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems, 10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants. Logistic regression analyses were conducted to examine the associations between statin/metformin/statin + metformin therapies and the incidence of neuropathy. Propensity score (PS) matching was performed on the basis of age, sex and comorbidities. RESULTS: Overall, 34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017, respectively. Statin therapy was associated with increased risks of neuropathy in 2016 and 2017 [PS-matched odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; PS-matched OR = 1.17, 95%CI: 1.03-1.33, respectively]. Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017 (PS-matched OR = 0.30, 95%CI: 0.21-0.42; PS-matched OR = 0.44, 95%CI: 0.32-0.60, respectively). Combined statin + metformin therapy was not significantly associated with neuropathy in 2016 or 2017 (PS-matched OR = 0.85, 95%CI: 0.61-1.19; PS-matched OR = 0.95, 95%CI: 0.66-1.38, respectively). CONCLUSION: Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM, but metformin therapy showed the opposite association.

15.
Diabetes Metab J ; 45(4): 461-481, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34352984

RESUMO

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.


Assuntos
Diabetes Mellitus , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Diabetes Mellitus/terapia , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , República da Coreia/epidemiologia , Sociedades Médicas
16.
Cell Metab ; 33(2): 334-349.e6, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33535098

RESUMO

Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPRmt) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of ß-endorphin (ß-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or ß-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/ß-END expression and induces adipose tissue UPRmt and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.


Assuntos
Hipotálamo/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Condicionamento Físico Animal , Pró-Opiomelanocortina/metabolismo , Animais , Linhagem Celular Tumoral , Metabolismo Energético , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
17.
Int J Obes (Lond) ; 45(4): 776-786, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33473176

RESUMO

OBJECTIVE: We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea. METHODS: People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values. RESULTS: The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m2, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m2 at 2 months; -4.23 kg and -1.55 kg/m2 at 4 months, and -5.14 kg and -1.89 kg/m2 at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%). CONCLUSIONS: In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.


Assuntos
Estilo de Vida , Liraglutida/uso terapêutico , Obesidade/terapia , Redução de Peso , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Exercício Físico , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
18.
Nat Commun ; 11(1): 5772, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188191

RESUMO

Hypothalamic neurons including proopiomelanocortin (POMC)-producing neurons regulate body weights. The non-motile primary cilium is a critical sensory organelle on the cell surface. An association between ciliary defects and obesity has been suggested, but the underlying mechanisms are not fully understood. Here we show that inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depleting ciliogenic genes IFT88 and KIF3A, leads to adulthood obesity in mice. In contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity. In developing POMC neurons, abnormal cilia formation disrupts axonal projections through impaired lysosomal protein degradation. Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in the hypothalamus of neonatal mice; through these effects they critically modulate the organization of hypothalamic feeding circuits. Our findings reveal a mechanism of early life programming of adult adiposity, which is mediated by primary cilia in developing hypothalamic neurons.


Assuntos
Adiposidade , Cílios/metabolismo , Hipotálamo/embriologia , Hipotálamo/metabolismo , Lisossomos/metabolismo , Animais , Animais Recém-Nascidos , Núcleo Arqueado do Hipotálamo/metabolismo , Axônios/metabolismo , Metabolismo Energético , Feminino , Glucose/metabolismo , Leptina/metabolismo , Desnutrição/patologia , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Neurogênese , Obesidade/metabolismo , Obesidade/patologia , Organogênese , Pró-Opiomelanocortina/metabolismo , Proteólise
19.
ACS Appl Mater Interfaces ; 10(35): 29730-29740, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30106270

RESUMO

Electromagnetic (EM) wave emissions from wearable or flexible smart display devices can cause product malfunction and have a detrimental effect on human health. Therefore, EM shielding strategies are becoming increasingly necessary. Consequently, herein, we prepared a transparent acrylic polymer-coated/reduced graphene oxide/silver nanowire (Ag NW) (A/RGO/SANW) EM interference (EMI) shielding film via liquid-to-vapor pressure-assisted wet sintering. The film exhibited enhanced Ag NW network formation and antireflection (AR) effects. The wet-sintered Ag NW shielding film had a threshold radius of curvature (ROC) of 0.31 mm at a film thickness of 100 µm, demonstrating its high flexibility, whereas the conventional indium tin oxide (ITO) shielding film had a threshold ROC of ∼5 mm. The EMI shielding effectiveness (SE) of the A/RGO/SANW multilayer film was approximately twice that of the ITO film at a similar relative transmittance (84-85%). The optical relative reflectance of the Ag NW layer was reduced due to the AR effect, and the visible-light transmittance was considerably improved owing to the different refractive indices in the multilayer shielding film. Because the acrylic coating layer had a high contact angle, the multilayer film exhibited high temperature and humidity durability with little change in the SE over 500 h at 85 °C and 85% relative humidity. The multilayer film comprising wet-sintered Ag NW exhibited high flexibility and humidity durability, high shielding performance (more than 24 dB at a relative transmittance of 85% or more), and high mass productivity, making it highly applicable for use as a transparent shielding material for future flexible devices.

20.
Endocrinol Metab (Seoul) ; 33(2): 245-251, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29766682

RESUMO

BACKGROUND: Blood levels of many hormones show rhythmic fluctuations with variable duration of cycles. Clusterin/apolipoprotein J is a glycoprotein which is highly expressed in the plasma and has modulatory roles in immune and inflammatory reactions, neurobiology, lipid metabolism, and leptin signaling. In this study, we examined the diurnal fluctuations of plasma clusterin concentrations in lean and obese young men. METHODS: For the study, 14 subjects (five lean and five obese men; two lean and two obese women) were admitted to the research ward and blood samples were drawn every 30 minutes during light-on period (6:00 AM to 10:00 PM) and every hour during light-off period. RESULTS: Notably, plasma clusterin concentrations displayed a unique ultradian rhythm with five cycles a day in both men and women. During the light-on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. In contrast, single oscillation curve during light-off exhibited a smoothened/lower peak and longer (8-hour) duration. In obese men, these cycles were phase-advanced by approximately 1 hour, and had reduced amplitude of fluctuating curves and blunted diurnal pattern. Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal-related cues. CONCLUSION: These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles.

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