• Integrative Medicine Research
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• v.2 no.4
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• pp.131-138
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• 2013

The skeletal muscle in our body is a major site for bioenergetics and metabolism during exercise. Carbohydrates and fats are the primary nutrients that provide the necessary energy required to maintain cellular activities during exercise. The metabolic responses to exercise in glucose and lipid regulation depend on the intensity and duration of exercise. Because of the increasing prevalence of obesity, recent studies have focused on the cellular and molecular mechanisms of obesity-induced insulin resistance in skeletal muscle. Accumulation of intramyocellular lipid may lead to insulin resistance in skeletal muscle. In addition, lipid intermediates (e.g., fatty acyl-coenzyme A, diacylglycerol, and ceramide) impair insulin signaling in skeletal muscle. Recently, emerging evidence linking obesity-induced insulin resistance to excessive lipid oxidation, mitochondrial overload, and mitochondrial oxidative stress have been provided with mitochondrial function. This review will provide a brief comprehensive summary on exercise and skeletal muscle metabolism, and discuss the potential mechanisms of obesity-induced insulin resistance in skeletal muscle.

• The Korean Journal of Food And Nutrition
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• v.30 no.4
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• pp.830-840
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• 2017

Excessive body weight gain during the growth period of early life may predispose individuals towards obesity and metabolic disorder in later life. We investigated the possibility of using the food efficiency ratio as an early indicator for predicting susceptibility to diet-induced obesity and insulin resistance. Four-week-old, prepubertal, male Sprague Dawley rats were divided into obesity-prone and obesity-resistant groups based on food efficiency ratio values after five days on a high-fat diet. Metabolic parameters measured after 2, 6, and 10 weeks, and specific phenotypes were compared with each group. Obesity-prone rats had higher increases in body weight and fat mass compared to obesity-resistant rats over the study period. Obesity-prone rats became glucose intolerant early in this study and remained so throughout the experimental period, with increases in fat weight and leptin levels occurring first, followed by increases in insulin level. Gluconeogenesis and insulin resistance significantly increased in obesity-prone groups in which activities of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were increased and glucokinase activity decreased. Higher food efficiency ratio at an early age was closely correlated with body fat accumulation, hyperleptinemia, and hyperinsulinemia of middle and elderly age. We suggest a high food efficiency ratio in prepubertal subjects may be a useful predictor of future obesity and insulin resistance.

• Clinical and Experimental Pediatrics
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• v.64 no.1
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• pp.12-20
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• 2021

The mean age at menarche (AAM) of Korean females has been rapidly decreasing over the last 50 years; currently, the prevalence of early menarche (<12 years) is 22.3%. Female adolescents who experience early menarche are known to be at greater risk of psychosocial and behavioral problems along with several physical health problems such as menstrual problems. They also tend to achieve a shorter final height and develop obesity. Population-based Korean studies have shown a strong association between early menarche and the risk of obesity, insulin resistance, metabolic syndrome, nonalcoholic fatty liver disease, diabetes, breast cancer, and cardiovascular disease in adulthood. Although the exact mechanism of how early menarche causes cardiometabolic derangement in later adulthood is unknown, childhood obesity and insulin resistance might be major contributors. Recent studies demonstrated that an excessive consumption of fructose might underlie the development of obesity and insulin resistance along with an earlier AAM. A positive association was observed between sugar-sweetened beverages (a major source of fructose) intake and obesity, metabolic syndrome, insulin resistance, and cardiometabolic risk in Korean females. In pediatrics, establishing risk factors is important in preventing disease in later life. In this regard, early menarche is a simple and good marker for the management of cardiometabolic diseases in adulthood. Decreasing one's fructose intake might prevent early menarche as well as the development of obesity, insulin resistance, and cardiometabolic diseases.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.73-76
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• 2012

More and more children are becoming obese and overweight due to several factors that include a high energy density in the diet (a high fat intake) and low energy expenditure. Consequently childhood obesity is becoming a significant health problem. Fat tissue releases many cytokines such as resistin, tumor necrosis factor-${\alpha}$, leptin, interleukin-6. These adipocytokines induce obesity-related insulin resistance. Insulin resistance is a key component of obesity-related metabolic problems such as hypertension, type 2 diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, acanthosis nigricans and polycystic ovarian syndrome. This review article focused on insulin resistance and its related metabolic diseases.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.364-365
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• 2012

Liver is the major organ to regulate the systemic glucose homeostasis and insulin resistance. Excess energy intake leads to triglyceride accumulation in adipose tissue first and subsequent accumulation in liver, resulting in obesity and type 2 diabetes. The representative pathological animal model for obesity associated insulin resistance is a high fat diet (HFD) fed mice model. Given the essential role of liver fat accumulation in developing systemic insulin resistance in obesity, I measured the liver triglyceride contents in HFD fed mice as a function of time. As such, in this report, I show the cause and effect relationship with regard to time during a HFD feeding between a variety of factors that are related to systemic insulin resistance including glucose intolerance, plasma insulin level and inflammatory gene expression in liver and adipose tissue.

• Nutrition Research and Practice
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• v.16 no.1
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• pp.46-59
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• 2022

BACKGROUND/OBJECTIVES: Aster yomena (Kitam.) Honda (AY) has remarkable bioactivities, such as antioxidant, anti-inflammation, and anti-cancer activities. On the other hand, the effects of AY against obesity-induced insulin resistance have not been reported. Therefore, this study examined the potential of AY against obesity-associated insulin resistance in high-fat diet (HFD)-fed mice. MATERIALS/METHODS: An obesity model was established by feeding C57BL/6J mice a 60% HFD for 16 weeks. The C57BL6/When ethyl acetate fraction from AY (EFAY) at doses of 100 and 200 mg/kg/day was administered orally to mice fed a HFD for the last 4 weeks. Normal and control groups were administered water orally. The body weight and fasting blood glucose were measured every week. Dietary intake was measured every other day. After dissection, blood and tissues were collected from the mice. RESULTS: The administration of EFAY reduced body and organ weights significantly compared to HFD-fed control mice. The EFAY-administered groups also improved the serum lipid profile by decreasing the triglyceride, total cholesterol, and low-density lipoprotein compared to the control group. In addition, EFAY ameliorated the insulin resistance-related metabolic dysfunctions, including the fasting blood glucose and serum insulin level, compared to the HFD-fed control mice. The EFAY inhibited lipid synthesis and insulin resistance by down-regulation of hepatic fatty acid synthase and up-regulation of the AMP-activated protein kinase pathway. EFAY also reduced lipid peroxidation in the liver, indicating that EFAY protected hepatic injury induced by obesity. CONCLUSIONS: These results suggest that EFAY improved obesity-associated insulin resistance by regulating the lipid and glucose metabolism, suggesting that AY could be used as a functional food to prevent obesity and insulin resistance.

• Molecules and Cells
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• v.47 no.3
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• pp.100007.1-100007.11
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• 2024

Recent evidence establishes a pivotal role for obesity-induced inflammation in precipitating insulin resistance and type-2 diabetes. Central to this process is the proinflammatory M1 adipose-tissue macrophages (ATMs) in epididymal white adipose tissue (eWAT). Notably, natural killer (NK) cells are a crucial regulator of ATMs since their cytokines induce ATM recruitment and M1 polarization. The importance of NK cells is shown by the strong increase in NK-cell numbers in eWAT, and by studies showing that removing and expanding NK cells respectively improve and worsen obesity-induced insulin resistance. It has been suggested that NK cells are activated by unknown ligands on obesity-stressed adipocytes that bind to NKp46 (encoded by Ncr1), which is an activating NK-cell receptor. This was supported by a study showing that NKp46-knockout mice have improved obesity-induced inflammation/insulin resistance. We therefore planned to use the NKp46-knockout mice to further elucidate the molecular mechanism by which NKp46 mediates eWAT NK-cell activation in obesity. We confirmed that obesity increased eWAT NKp46⁺ NK-cell numbers and NKp46 expression in wild-type mice and that NKp46-knockout ablated these responses. Unexpectedly, however, NKp46-knockout mice demonstrated insulin resistance similar to wild-type mice, as shown by fasting blood glucose/insulin levels and glucose/insulin tolerance tests. Obesityinduced increases in eWAT ATM numbers and proinflammatory gene expression were also similar. Thus, contrary to previously published results, NKp46 does not regulate obesity-induced insulin resistance. It is therefore unclear whether NKp46 participates in the development of obesity-induced inflammation and insulin resistance. This should be considered when elucidating the obesity-mediated molecular mechanisms that activate NK cells.

• BMB Reports
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• v.42 no.8
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• pp.475-481
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• 2009

Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer's disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production.

• The Journal of Internal Korean Medicine
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• v.37 no.4
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• pp.609-623
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• 2016

Objective: This study was undertaken to investigate the effects of Mori folium on insulin resistance and adipose tissue inflammation in an experimental mouse model of obesity.Methods: Obesity was induced in C57BL/6 mice by feeding them a high-fat diet. The mice were divided into four groups (n=6): a normal diet, high-fat diet, high-fat diet with 40 mg of Mori folium, and high-fat diet with 800 mg of Mori folium groups. After 13 wk, the body weights, fasting blood glucose and fasting serum insulin levels, insulin resistance (homeostatic model assessment) levels, oral glucose tolerance test levels, epididymal fat and liver weights, and gene expression of tumor necrosis factor-α, interleukin-6, and interferon-γ were measured. In addition, adipose tissue macrophages were analyzed by fluorescence-activated cell sorting.Results: Mori folium significantly reduced blood glucose levels, oral glucose tolerance levels, and liver weights. It also reduced adipose tissue macrophage numbers and tumor necrosis factor receptor-α gene expression.Conclusions: These results show that Mori folium has insulin resistance reduction and anti-inflammatory effects in an experimental mouse model of obesity.

• Journal of the East Asian Society of Dietary Life
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• v.19 no.5
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• pp.713-722
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• 2009

Vitamin D levels have been reported to be associated with diabetes, obesity and metabolic syndrome. There have been studies on the nutritional status of vitamin D in postmenopausal women at Seoul and premenopausal women at Busan, and these studies showed that nearly no relationship between serum vitamin D levels and the obesity index existed. However, there have been no studies that examined about the relationship between serum vitamin D levels and insulin resistance in Korea. In this study, we investigated serum vitamin D levels and the relationship between serum vitamin D levels and insulin resistance (homeostasis model assessment of insulin resistance), obesity index (body mass index, percentage of body fat and waist circumference) in 180 premenopausal women (non-obese women 87.8%, obese women 12.2%) in spring (March~April), fall (September~October) and winter (January~February) at Daejeon. Serum vitamin D levels were lower in winter than in spring-fall, after adjusting for age and the obesity index. The frequency of vitamin D inadequacy (serum vitamin D levels were $\leq$ 20 ng/mL) was 45.5% in winter and, 23.5% in spring-fall, and which showed that vitamin D inadequacy was higher in winter than in spring-fall. Multiple regression analysis showed that serum vitamin D levels had no relationship with the obesity index or insulin resistance. There was no difference in the obesity index or insulin resistance between the vitamin D inadequacy and normal group, and there was no relationship between serum vitamin D levels and the obesity index or insulin resistance in non-obese and obese premenopausal women, respectively. In conclusion, serum vitamin D levels in premenopausal women at Daejeon were lower in winter than in spring-fall, and the frequency of vitamin D inadequacy was higher in winter than in spring-fall. Serum vitamin D levels had no relationship with the obesity index or insulin resistance in premenopausal women, most of whom were not obese.