Minchul Seo

Association of periodontitis with insulin resistance, β-cell function, and impaired fasting glucose before onset of diabetes

Periodontitis and insulin resistance (IR) show bidirectional relationship. No studies have assessed the associations of periodontitis with IR, impaired β-cell function, and impaired fasting glucose (IFG) in the general population. We investigated these associations in a representative sample of the Korean population. The subjects were 8,248 males and 10,874 females, who were ≥ 20 years of age and participants in the third, fourth, and fifth Korea National Health and Nutritional Examination Surveys (2008-2010). Periodontitis was defined as community periodontal index (CPI) ≥ code 3 according to World Health Organization criteria. Homeostasis model assessments of IR and β-cell function (HOMA-IR and HOMA-β) were calculated. Participants with periodontitis showed a higher prevalence of diabetes than those without periodontitis. Among subjects without diabetes, after adjustment for confounding factors including age, gender, body mass index, systolic blood pressure, serum total cholesterol, smoking status, alcohol consumption, region, and regular exercise, a comparison of participants with periodontitis vs those without showed a significantly higher prevalence of IFG (28.5% vs. 17.7%, p<0.001) and lower HOMA-β (115.2 vs. 130.8, p<0.001). Periodontitis was identified as a risk factor for IFG (OR, 1.301; 95% CI, 1.193∼1.418; p<0.001). Conversely, participants with and without periodontitis had similar HOMA-IR. In conclusion, periodontitis showed an association with decreased β-cell function and increased prevalence of IFG before onset of diabetes as well as increased prevalence of diabetes in the Korean population. Future longitudinal studies are warranted to elucidate the shared pathophysiology between periodontal disease and diabetes mellitus.

Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress.

Tenebrio molitor Larvae Inhibit Adipogenesis through AMPK and MAPKs Signaling in 3T3-L1 Adipocytes and Obesity in High-Fat Diet-Induced Obese Mice

Despite the increasing interest in insect-based bioactive products, the biological activities of these products are rarely studied adequately. Larvae of Tenebrio molitor, the yellow mealworm, have been eaten as a traditional food and provide many health benefits. Therefore, we hypothesized that T. molitor larvae might influence adipogenesis and obesity-related disorders. In the present study, we investigated the anti-adipogenic and antiobesity effects of T. molitor larvae in vitro and in vivo. The lipid accumulation and triglyceride content in mature adipocytes was reduced significantly (up to 90%) upon exposure to an ethanol extract of T. molitor larvae, without a reduction in cell viability. Exposure also resulted in key adipogenic and lipogenic transcription factors. Additionally, in adipogenic differentiation medium the extract induced phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and mitogen-activated protein kinases. Daily oral administration of T. molitor larvae powder to obese mice fed high-fat diet attenuated body weight gain. We also found that the powder efficiently reduced hepatic steatosis as well as aspartate and alanine transaminase enzyme levels in mice fed a high-fat diet. Our results suggest that T. molitor larvae extract has an antiobesity effect when administered as a food supplement and has potential as a therapeutic agent for obesity.

Algae Undaria pinnatifida Protects Hypothalamic Neurons against Endoplasmic Reticulum Stress through Akt/mTOR Signaling

Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence has suggested that Undaria pinnatifida (UP), an edible brown algae, has antioxidant activity. However, the neuroprotective effect of UP has yet to be examined. In this study, to investigate the neuroprotective effect of UP on ER stress-induced neuronal damage in mouse hypothalamic neurons, mice immortal hypothalamic neurons (GT1-7) were incubated with extract of UP. ER stress was induced by treating with tunicamycin. Tunicamycin induced apoptotic cell death was compared with the vehicle treatment through excessive ER stress. However UP protected GT1-7 cells from cell death, occurring after treatment with tunicamycin by reducing ER stress. Treatment with UP resulted in reduced increment of ATF6 and CHOP, and recovered the decrease of phosphorylation of Akt/mTOR by tunicamycin and the increment of autophagy. These results show that UP protects GT1-7 cells from ER stress induced cell death through the Akt/mTOR pathway. The current study suggests that UP may have a beneficial effect on cerebral neuronal degeneration in metabolic diseases with elevated ER stress.

Association of hearing impairment with insulin resistance, β-cell dysfunction and impaired fasting glucose before onset of diabetes.

Diabetes is a known risk factor for hearing impairment. No study regarding the association of insulin resistance (IR), β–cell dysfunction and impaired fasting glucose (IFG) with hearing impairment has been reported in the population without diabetes. We examined these associations using a representative sample of the Korean population.

Acute anti-obesity effects of intracerebroventricular 11β-HSD1 inhibitor administration in diet-induced obese mice

The hypothalamus is the regulatory centre of both appetite and energy balance and endoplasmic reticulum (ER) stress in the hypothalamus is involved in the pathogenesis of obesity. Recently, inhibition of 11 β hydroxysteroid dehydrogenase type1 (11β‐HSD1) was reported to have an anti‐obesity effect by reducing fat mass. However, the link between the role of 11β‐HSD1 in the hypothalamus and obesity has yet to be determined. In the present study, embryonal primary hypothalamic neurones and high‐fat diet (HFD) fed mice were used to investigate the anorexigenic effects of 11β‐HSD1 inhibitors both in vitro and in vivo. In hypothalamic neurones, carbenoxolone (a non selecitve 11β‐HSD inhibitor) alleviated ER stress and ER stress‐induced neuropeptide alterations. In HFD mice, i.c.v. administration of carbenoxolone or KR67500 (nonselective and selective 11β‐HSD1 inhibitors, respectively) was associated with less weight gain compared to control mice for 24 hours after treatment, presumably by reducing food intake. Furthermore, glucose regulated protein (Grp78), spliced X‐box binding protein (Xbp‐1s), c/EBP homologous protein (chop) and ER DnaJ homologue protein (Erdj4) expression was decreased in the hypothalami of mice administrated 11β‐HSD1 inhibitors compared to controls. Conversely, the phosphorylation of protein kinase B (PKB/Akt), signal transducer and activator of transcription 3 (Stat3), mitogen‐activated protein kinase (MAPK/ERK) and S6 kinase1 (S6K1) in the hypothalamus was induced more in mice treated using the same regimes. In conclusion, acute 11β‐HSD1 inhibition in the hypothalamus could reduce food intake by decreasing ER stress and increasing insulin, leptin, and mammalian target of rapamycin complex 1 (mTORC1) signalling.

Effects of the Various Cooling Conditions on 1,064-nm nd:Yag Laser Treatment for Selective Photothermolysis

The purpose of this study was to find optimum treatment conditions for selective photothermolysis by evaluating internal–external heat distributions according to different cooling methods. The 1,064-nm Nd:YAG laser was transmitted into a skin-mimicking phantom with different cooling conditions, and its minimum temperatures and sub-zero times were measured. The cooling methods were classified into a total of eight conditions composed of five cryogen spray cooling conditions and three air cooling conditions. Based on the experimental results, condition 2 was selected as the optimum cooling condition for selective photothermolysis obtained from the cryogen spray cooling method.