Primary Cilia as a Signaling Platform for Control of Energy Metabolism

Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.

Differentiation between polycystic ovary syndrome and polycystic ovarian morphology by means of an anti-Müllerian hormone cutoff value

BACKGROUND/AIMS: Although increased serum anti-Müllerian hormone (AMH) level has been suggested to be a surrogate marker of polycystic ovarian morphology (PCOM), its association with polycystic ovary syndrome (PCOS) is controversial, and its diagnostic value has not been determined. We aimed to observe the relationship between the AMH level and PCOS phenotypes and to determine the optimal cutoff value of AMH for the diagnosis of PCOS in young Korean women. METHODS: We recruited 207 women with PCOS (120 with PCOM and 87 without PCOM) and 220 regular cycling women with normoandrogenemia (100 with PCOM and 120 without PCOM). Subjects underwent testing at a single outpatient visit. Serum AMH level was measured. RESULTS: Women with PCOS had higher serum AMH levels than did regular cycling women with normoandrogenemia (p < 0.05). Women with PCOM had higher serum AMH levels than women without PCOM, regardless of PCOS status (p < 0.05). The optimal AMH cutoff value for the diagnosis of PCOS was 10.0 ng/mL (71% sensitivity, 93% specificity). Serum AMH was an independent determinant of total testosterone after adjustment for age, body mass index, and the number of menses/year (β = 0.31, p < 0.01). An association between AMH and hyperandrogenism was only observed in women with PCOS, and it was independent of the presence of PCOM. CONCLUSION: The serum AMH level can be useful for the diagnosis of PCOS at any age less than 40 years, and the optimal cutoff value for the diagnosis of PCOS identified in this study of young Korean women was 10.0 ng/mL.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

PURPOSE: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. MATERIALS AND METHODS: We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). RESULTS: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

PURPOSE: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. MATERIALS AND METHODS: We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). RESULTS: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Increased Epicardial Adipose Tissue Thickness in Type 2 Diabetes Mellitus and Obesity

BACKGROUND: Epicardial adipose tissue (EAT) is suggested to play an important role in the progression of metabolic syndrome. We aimed to establish a simple method to measure EAT and examine the differences in EAT thickness according to the presence of type 2 diabetes mellitus or obesity. METHODS: A total of 94 patients (42.6% type 2 diabetes mellitus, 53.2% obese, mean age 61+/-13) who underwent multidetector computed tomography were enrolled. Thickness of EAT was measured on the parasternal short and horizontal long axis view. Epicardial fat area (EFA) was measured at the level of left main coronary artery (LMCA). RESULTS: All EAT thicknesses were correlated with EFA at the LMCA level (r=0.235 to 0.613, all Ps<0.05), and EAT thickness in the left atrioventricular groove (LAVG) had the highest correlation coefficient (r=0.613). EFA, and EAT thicknesses in the LAVG and the left ventricular apex were higher in the group with type 2 diabetes mellitus than in the group without type 2 diabetes mellitus when adjusted only for body mass index. When adjusted only for type 2 diabetes mellitus, EFA, and EAT thicknesses in the LAVG and the right atrioventricular groove were higher in obese group than in nonobese group. CONCLUSION: In conclusion, EAT thickness can be easily measured and represent EFA. EAT thickness, especially in LAVG, was higher in groups with type 2 diabetes mellitus and obesity independently. These findings implicate that EAT thickness may be a useful indicator for type 2 diabetes mellitus and obesity.

FTO Gene Variants Are Associated with PCOS Susceptibility and Hyperandrogenemia in Young Korean Women

BACKGROUND: The fat mass and obesity-associated (FTO) gene is associated with obesity and type 2 diabetes mellitus. Obesity and insulin resistance are also common features of polycystic ovary syndrome (PCOS). Therefore, the FTO gene might be a candidate gene for PCOS susceptibility. The aim of the present study was to evaluate the effects of FTO gene variants on PCOS susceptibility and metabolic and reproductive hormonal parameters. METHODS: We recruited 432 women with PCOS (24+/-5 years) and 927 healthy women with regular menstrual cycles (27+/-5 years) and performed a case-control association study. We genotyped the single nucleotide polymorphisms rs1421085, rs17817449, and rs8050136 in the FTO gene and collected metabolic and hormonal measurements. RESULTS: Logistic regression revealed that the G/G genotype (rs1421085, 1.6%), the C/C genotype (rs17817449, 1.6%), and the A/A genotype (rs8050136, 1.6%) were strongly associated with an increased risk of PCOS (odds ratio, 2.551 to 2.559; all P<0.05). The strengths of these associations were attenuated after adjusting for age and BMI. The women with these genotypes were more obese and exhibited higher free androgen indices (P<0.05) and higher free testosterone levels (P=0.053 to 0.063) compared to the other genotypes. However the significant differences disappeared after adjusting for body mass index (BMI). When we analyzed the women with PCOS and the control groups separately, there were no significant differences in the metabolic and reproductive hormonal parameters according to the FTO gene variants. CONCLUSION: The rs1421085, rs17817449, and rs8050136 variants of the FTO gene were associated with PCOS susceptibility and hyperandrogenemia in young Korean women. These associations may be mediated through an effect of BMI.

Obesity: Introduction / 대한내과학회지

Obesity is defined as abnormal or excessive fat accumulation that presents a risk to a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Therefore, obesity is associated with decreases in life expectancy. Also weight loss of 5-10% is associated with clinically significant health benefits. In Korea, a person with a body mass index of 25 kg/m2 or more is considered obese. In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended screening all adults for obesity and USPSTF advised that clinicians offer or refer patients with obesity to intensive, multicomponent behavioral interventions. In Korea, management of obesity 2010 recommendation was published but there is no recommendation about screening for obesity. Because of the increasing prevalence of obesity, new recommendations on screening and efficient treatment for obesity and overweight are needed in Korea.

A Case of Double Primary Cancers in the Esophagus and Stomach / 이화의대지

Double primary cancers are two independently developed cancers in an individual. There have been some reports on double primary cancer since Billroth reported it for the first time in 1879. Double primary cancer of the stomach and esophagus has been revealed a very low incidence worldwide. The incidence of an esophageal cancer with another primary cancer is reported to be 9.5~27%, but double primary cancers in the esophagus and stomach have been rarely reported to our knowledge. In this study, we present here a case of double primary esophageal and stomach cancer in a 66-year-old man because of progressive dysphagia.

A Case of Jejunal Gastrointestinal Stromal Tumor Diagnosed by Videocapsule Endoscopy and Single-Balloon Enteroscopy / 이화의대지

Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors that arise in the wall of the gastrointestinal tract. We report a case of obscure gastrointestinal bleeding due to a GIST of the jejunum successfully documented by videocapsule endoscopy (VCE) and single-balloon enteroscopy (SBE). A 36-year-old man with hematochezia was referred for further evaluation of no evidence of bleeding focus on esophagogastroduodenoscopy and colonoscopy. A VCE showed a suspicious ulcerative hyperemic mass that located in about 1 hour apart from duodenal second portion. SBE revealed a nonbleeding 4x2 cm mass with an ulcer at the proximal jejunum. The patient underwent laparoscopic resection without complication. Histological examination revealed a well circumscribed, dumbbell-shaped firm mass comprised of spindle cells. Immunohistochemical staining for CD 117 was diffusely positive, whereas staining for S-100, CD 34 and MIB-1 was all negative. It was confirmed to be a low-grade GIST at the proximal jejunum.