Hyeong Kyu Park

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases.

Resistin in Rodents and Humans

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

Changes of Mitochondrial DNA Content in the Male Offspring of Protein‐Malnourished Rats

Abstract: Nutritional deprivation of the fetus and infant is associated with susceptibility to the development of impaired glucose tolerance or type 2 diabetes in adult life. Quantitative changes in mitochondrial DNA (mtDNA) seem to be associated with type 2 diabetes, but the effect of protein malnutrition on mtDNA content is not known. This study investigated the effects of protein malnutrition in fetus and early life on mtDNA content and glucose‐insulin metabolism in adult life. Male offspring of dams fed a low‐protein (LP) diet (8% casein) during pregnancy and lactation were weaned onto either a control (18% casein) diet (recuperated group, R) or a LP diet, and they were compared with the control group (C). The mtDNA content in the liver was lower in the R and LP groups than in the C group at 5 weeks of age, but higher in the R and LP groups than in the C group at 15 weeks of age. The mtDNA content in skeletal muscle and pancreas was significantly lower in the R and LP groups than in the C group at 25 weeks of age. Fetal‐malnourished rats showed decreased pancreatic β‐cell mass and reduced insulin secretory responses to glucose load, but no differences in glucose tolerance or insulin sensitivity. Our findings imply that protein malnutrition in utero causes changes in mtDNA content, impaired β‐cell development, and insulin secretion, which may contribute to the development of type 2 diabetes in later life.

Increased Expression of Focal Adhesion Kinase in Thyroid Cancer: Immunohistochemical Study

Focal adhesion kinase (FAK) is a tyrosine kinase that is found in cellular structures called focal adhesions. FAK appears to be a key element in signal transduction pathways involved in cell adhesion and locomotion. FAK is overexpressed in various tumors, including tumors derived from regions of the head and neck, colon, breast, prostate, and liver. In this study, we investigated immunohistochemically whether FAK expression was increased in thyroid cancers. FAK staining was not seen in any of the 20 normal thyroid tissues or the 6 nodular hyperplasia specimens. In contrast, FAK staining was observed in all of 17 papillary carcinomas, 9 follicular carcinomas, 8 medullary carcinomas, and 2 anaplastic carcinomas. Nine of 17 follicular adenomas showed FAK immunoreactivity. FAK was not expressed in normal tissue and nodular hyperplasia, but was expressed in some of the follicular adenoma, and all of the follicular, papillary, medullary and anaplastic thyroid carcinoma. This result indicates that the up-regulation of FAK may play a role in the development of thyroid carcinogenesis.

Connecting Myokines and Metabolism

Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets.

Linking resistin, inflammation, and cardiometabolic diseases

Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.

Triiodothyronine Levels Are Independently Associated with Metabolic Syndrome in Euthyroid Middle-Aged Subjects

Background Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. Methods A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. Results Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders. Conclusion Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.

Number of tumor foci as predictor of lateral lymph node metastasis in papillary thyroid carcinoma

The purpose of this study was to determine the clinicopathologic characteristics of patients with papillary thyroid carcinoma (PTC) by the number of tumor foci.

Association of Triiodothyronine Levels with Future Development of Metabolic Syndrome in Euthyroid Middle-aged Subjects: A 6-Year Retrospective Longitudinal Study

BACKGROUND Several cross-sectional studies have reported that thyroid hormone levels are associated with cardiovascular risk markers and metabolic syndrome (MetS) even in euthyroid subjects. However, the prognostic role of serum thyroid hormone levels in the risk of incident MetS has not been elucidated. AIM We aimed to investigate the associations of baseline serum thyroid hormone levels with the development of MetS in healthy subjects. METHODS This 6-year, cross-sectional, longitudinal and follow-up study was conducted in 12 037 euthyroid middle-aged subjects without MetS subjected to comprehensive health examinations. Subjects were grouped according to total triiodothyronine (T3) quartiles. The hazard ratio (HR) for the development of MetS according to T3 quartiles was estimated using Cox proportional hazards model. RESULTS During the 6-year period, 3544 incident cases of MetS (29%) were identified. The proportion of subjects with incident MetS increased across the T3 quartiles (P for trend <0.001). The HR and 95% confidence interval (CI) for the development of MetS were significantly higher in the highest T3 quartile compared with the lowest T3 quartile even after adjusting for confounding variables including gender, age and smoking (HR: 1.238, 95% CI: 1.128-1.358, P < 0.001). CONCLUSION In euthyroid middle-aged subjects, serum T3 levels are associated with increased risk for future development of MetS.

Endoscopic comparison of alendronate alone and the enteric-coated alendronate with calcitriol combination in postmenopausal Korean females.

Background/Aims This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 µg) combined drug (Maxmarvil, Yuyu Co.). Methods The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 ± 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. Results Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. Conclusions The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.