Hong-Kyu Lee

Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase

AMP-activated protein kinase (AMPK) functions as a fuel sensor in the cell and is activated when cellular energy is depleted. Here we report that α-lipoic acid (α-LA), a cofactor of mitochondrial enzymes, decreases hypothalamic AMPK activity and causes profound weight loss in rodents by reducing food intake and enhancing energy expenditure. Activation of hypothalamic AMPK reverses the effects of α-LA on food intake and energy expenditure. Intracerebroventricular (i.c.v.) administration of glucose decreases hypothalamic AMPK activity, whereas inhibition of intracellular glucose utilization through the administration of 2-deoxyglucose increases hypothalamic AMPK activity and food intake. The 2-deoxyglucose-induced hyperphagia is reversed by inhibiting hypothalamic AMPK. Our findings indicate that hypothalamic AMPK is important in the central regulation of food intake and energy expenditure and that α-LA exerts anti-obesity effects by suppressing hypothalamic AMPK activity.NOTE: In the version of this article initially published online, the name of an author was misspelled. The name of the twelfth author should be “Benoit Viollet”. This error has been corrected for the HTML and print versions of the article

Changes in ghrelin and ghrelin receptor expression according to feeding status

&NA; Ghrelin, a newly identified gut hormone, has been implicated in the regulation of food intake and energy homeostasis. This study was undertaken to investigate changes in expression levels of stomach ghrelin as well as of ghrelin receptor in the hypothalamus and pituitary glands according to feeding state. Stomach ghrelin mRNA levels were increased by 48 h fasting but decreased by re‐feeding. The ghrelin receptor mRNA levels of 48h fasted rats were 8 times higher in the hypothalamus and 3 times higher in the anterior pituitary gland than levels in fed rats. In summary, not only stomach ghrelin, but also hypothalamic ghrelin receptor mRNA expression, increased during a fast. Such as enhanced ghrelin receptor expression could contribute to the amplification of ghrelin action in a negative‐energy balance state.

Prevalence of Diabetes and IGT in Yonchon County, South Korea

OBJECTIVE To determine the prevalence of diabetes and impaired glucose tolerance (IGT) in Yonchon County of South Korea and to investigate their associated factors. RESEARCH DESIGN AND METHODS We performed a population-based cross-sectional study with random cluster sampling of residents ≥30 years of age. Among the 3,804 residents sampled, a total of 2,520 participants had a standard 75-g oral glucose tolerance test and answered a detailed questionnaire. We also collected standard anthropometric data. RESULTS If the data for participants in the age range of 30–64 years were adjusted to the standard world population, the prevalence of diabetes was 7.2% and the prevalence of IGT was 8.9%. It was observed that the significant factors associated with diabetes were waist-to-hip circumference ratio, serum triglyceride levels, age, systolic blood pressure, family history of diabetes, and locality. CONCLUSIONS The prevalence of diabetes in Yonchon County was substantially higher than was previously suggested. The risk of diabetes increased with the increased central obesity and metabolic disturbances associated with insulin resistance.

The Low Prevalence of Immunogenetic Markers in Korean Adult-Onset IDDM Patients

OBJECTIVE IDDM is an autoimmune disease that occurs among genetically susceptible individuals. In Asian populations, it is not uncommon for adult patients with NIDDM to eventually lose β-cell function and develop IDDM. These individuals may be characterized by autoantibodies to GAD and high-risk HLA-DQ alleles, which are unlikely to be prevalent among patients with true NIDDM or in the general population. The objective of the present study was to evaluate and compare the prevalence of these immunogenetic markers in NIDDM patients and healthy nondiabetic individuals from Korea. RESEARCH DESIGN AND METHODS The prevalences of anti-GAD antibodies and HLA-DQA1 and DQB1 alleles among 121 patients with newly diagnosed NIDDM identified from a population-based study in Yonchon, Korea, and 100 matched healthy control subjects were evaluated and compared. RESULTS The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 control subjects had a positive test for antibodies. Among those who tested positive, titers of antibodies to GAD were not high. No statistically significant differences in the distributions of either mean levels of anti-GAD antibodies or DQA1 and DQB1 alleles were found comparing NIDDM patients with control subjects. Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles in the Korean adult control population was similar to that in the U.S. white population (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). CONCLUSIONS The low prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility alleles among recent-onset NIDDM patients, which was similar to observations in control subjects, suggests that diabetes in Korean adults is unlikely to have an autoimmune component to its pathogenesis.