The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

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Insulin signalling and the regulation of glucose and lipid metabolism

Obesity is a principal causative factor in the development of metabolic syndrome. Here we report that increased oxidative stress in accumulated fat is an important pathogenic mechanism of obesity-associated metabolic syndrome. Fat accumulation correlated with systemic oxidative stress in humans and mice. Production of ROS increased selectively in adipose tissue of obese mice, accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes. In cultured adipocytes, elevated levels of fatty acids increased oxidative stress via NADPH oxidase activation, and oxidative stress caused dysregulated production of adipocytokines (fat-derived hormones), including adiponectin, plasminogen activator inhibitor-1, IL-6, and monocyte chemotactic protein-1. Finally, in obese mice, treatment with NADPH oxidase inhibitor reduced ROS production in adipose tissue, attenuated the dysregulation of adipocytokines, and improved diabetes, hyperlipidemia, and hepatic steatosis. Collectively, our results suggest that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.

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Increased oxidative stress in obesity and its impact on metabolic syndrome

Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5'-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full-length Ad in the liver. In parallel with its activation of AMPK, Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Blocking AMPK activation by dominant-negative mutant inhibits each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK. Our data may provide a novel paradigm that an adipocyte-derived antidiabetic hormone, Ad, activates AMPK, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo.

Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase

TLR4 is the receptor for LPS and plays a critical role in innate immunity. Stimulation of TLR4 activates proinflammatory pathways and induces cytokine expression in a variety of cell types. Inflammatory pathways are activated in tissues of obese animals and humans and play an important role in obesity-associated insulin resistance. Here we show that nutritional fatty acids, whose circulating levels are often increased in obesity, activate TLR4 signaling in adipocytes and macrophages and that the capacity of fatty acids to induce inflammatory signaling in adipose cells or tissue and macrophages is blunted in the absence of TLR4. Moreover, mice lacking TLR4 are substantially protected from the ability of systemic lipid infusion to (a) suppress insulin signaling in muscle and (b) reduce insulin-mediated changes in systemic glucose metabolism. Finally, female C57BL/6 mice lacking TLR4 have increased obesity but are partially protected against high fat diet-induced insulin resistance, possibly due to reduced inflammatory gene expression in liver and fat. Taken together, these data suggest that TLR4 is a molecular link among nutrition, lipids, and inflammation and that the innate immune system participates in the regulation of energy balance and insulin resistance in response to changes in the nutritional environment.

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TLR4 links innate immunity and fatty acid–induced insulin resistance

Adipose tissue as an endocrine organ.

Historical Overview Many nutrients are presently recognized to play an important role in human nutrition not only because they are essential for growth and maintenance of health, but also because they play an important role in the reduction of risk of noncommunicable diseases. The values of nutrient intakes that make allowance for individual variation in requirements and provide a margin of safety above the minimal requirement to prevent deficiencies have traditionally formed the basis for the establishment of the Recommended Dietary Allowances (RDAs). Preliminary values for nutrient requirements for Japanese were first described in 1926 in the book Nutrition by Dr. Tadasu Saiki (1), the founder of the National Institute of Nutrition (presently National Institute of Health and Nutrition) in Japan. The National Institute of Nutrition played a key role in conducting basic scientific studies and developing nutrient requirements for Japanese. In responce to food shortage resulting from World War II, some national organizations created nutritional standards independently for Japanese until around 1945. Since then nutritional standards for Japanese have been developed by the Prime Minister’s Office (presently Cabinet Office, government of Japan) and the Science and Technology Agency (presently Ministry of Education, Culture, Sports, Science and Technology) to promote growth, to maintain health and physical strength, and to improve work efficiency. From 1969, the Ministry of Health and Welfare became the presiding ministry to create RDAs in Japan (2). The RDAs used for the time period 1970–1975 were officially established by six committees. As shown in Table 1, RDAs was subsequently revised every five years until 2005 for the purpose of improving physique and corresponding to changes in population structure, economy or dietary habits (2–8). The concept of Dietary Reference Intakes was first introduced in the 6th revision of the RDAs (2000–2005) (8). In order to more comprehensively follow the approach used in devising the 6th revision of the RDAs, the 7th revision was established as the “Dietary Reference Intakes for Japanese (DRIs-J) 2005” by the Ministry of Health, Labour and Welfare (MHLW) (9). These DRIs-J were based on a systematic review of the evidence. The current version, “DRIs-J 2010,” was created based on the Health Promotion Law by the MHLW (10). DRIs-J expanded on the basic theories of the US/Canadian DRIs in order to create DRIs that are specific to the Japanese population. The DRIs-J were designed not only to prevent energy or nutrient deficiencies that may be caused by insufficient intake of energy or nutrients, but also for the primary prevention of lifestyle-related diseases caused by excess and/or imbalanced consumption of energy and nutrients. DRIs-J consists of six reference values (one for energy and five for nutrients) for the prevention of deficiencies, adverse effects by excess intake, and lifestyle-related diseases. In addition, the recommended dietary intake level is shown as a range rather than a singular value.

Historical Overview of the Establishment of Dietary Reference Intakes for Japanese

Survivors of the Great East Japan Earthquake in 2011 had higher risks of cardiovascular diseases and hypertension, particularly residents of heavy flooding areas and evacuees. Thus far, the association between the prevalence of hypertension and dairy consumption remains unknown among these evacuees. We investigated this association by housing type after the Great East Japan Earthquake. In this cross-sectional study, we conducted a baseline survey among 9569 survivors of the earthquake, aged ≥18 years, between September 2011 and February 2012. Hypertension was defined as a systolic/diastolic blood pressure ≥140/90 mmHg or as persons undergoing treatment for high blood pressure. The frequency of dairy consumption was determined using a questionnaire. Participants living in prefabricated housing and emergency shelters were regarded as residents of temporary housing. Hypertension was prevalent among 43.8% and 44.7% of the participants in temporary and non-temporary housing, respectively. A logistic regression analysis of the prevalence of hypertension by daily dairy consumption showed that the magnitude of multivariable-adjusted odds ratios differed according to housing type (odds ratio, 0.64; 95% confidence interval, 0.51-0.80 in temporary housing; odds ratio, 0.85; 95% confidence interval, 0.73-0.995 in non-temporary housing; P for interaction = 0.0501). These associations were consistent across subgroups according to sex, age, behavioral factors, obesity, disorders of lipid metabolism, and economic status. A higher frequency of dairy consumption was associated with a lower prevalence of hypertension among community-dwelling survivors of earthquakes and tsunamis, particularly those living in temporary housing. Therefore, dietary therapy involving dairy consumption could help prevent hypertension among evacuees.

Association between the prevalence of hypertension and dairy consumption by housing type among survivors of the Great East Japan Earthquake.

Objectives To assess the improvement of the menus by the meal providing system in emergency shelters, we reanalyzed the data obtained from the dietary survey at emergency shelters in the Miyagi Prefecture one month after the Great East Japan Earthquake in 2011.Methods We performed secondary use of the dietary survey conducted by the Miyagi prefectural government. In total, 386 emergency shelters participated in the dietary survey of one day in April 2011. We examined the meal providing system (the frequency of meals per day, the frequency of mass feeding for evacuees per day, and menu creators) and the menus at each emergency shelter (260). We classified menus into the following five groups: staple foods, main dishes, side dishes, dairy products, and fruits, and calculated the frequency of provision per day.Results There was no emergency shelter that provided zero or one meal per day. Compared with the emergency shelters that provided two meals per day, shelters that provided three had a significantly higher provision frequency of staple foods. However, there were no significant differences in the provision frequencies of the other four food groups between the shelters with two or three meals per day. In emergency shelters with a higher frequency of mass feeding for evacuees, the provision frequency of four food groups (staple foods, main dishes, side dishes, and fruits) was significantly higher compared to shelter with a lower frequency of mass feeding for evacuees. Furthermore, in the emergency shelters where dietitians created menus, the provision frequency for two food groups (dairy products and fruits) was significantly higher compared to shelters without dietitians.Conclusion A high frequency of mass feeding for evacuees resulted in a high provision frequency of main dishes, side dishes, and fruits, which can be limited in supply after a disaster. Also, in the emergency shelters where dietitians created menus, the provision frequency of dairy products and fruits was higher than in those without dietitians. These results suggested that diets in the emergency shelters may be improved by mass feeding and the involvement of dietitians.

The effects of changes in the meal providing system on emergency shelter menus following the Great East Japan Earthquake.

The need for food and nutrition assistance has increased due to the frequent occurrence of disasters and pandemics, such as coronavirus disease 2019 (COVID-19). However, after a disaster, food and nutrition are insufficient in terms of quantity and quality. In the case of the Great East Japan earthquake, the improvement factors for food and nutrition at emergency shelters included 1) emergency shelter size and equipment, 2) provision and content of meals, 3) collaboration among professionals, and 4) cooperation between shelters. However, there were hygiene and oral health problems, and dispatched dietitians had problems with nutrition assistance. The hygiene problems included 1) food, 2) cooking environment, 3) water supply and discharge, and 4) living space. In addition, oral health problems included 1) difficulty swallowing, 2) difficulty chewing, 3) environmental degradation, and 4) degradation of the oral condition. The problematic points of dispatched dietitians included the support provided not necessarily being consistent with needs, operational deficiencies at both the dispatching and receiving sides, and the short period of support. "Enthusiasm" can be a source of encouragement and a burden. To solve these problems, a training system for disaster dietitians and certification systems for disaster food have been established in Japan. Since the Great East Japan earthquake, various kinds of evidence and actions have been taken, and nutritional problems after disasters have gradually improved. Therefore, it seems that advanced actions and standards should be set not only in Japan but also globally.

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Frontiers in Disaster Nutrition: Evidence to Action.

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Nobuyo Tsuboyama-Kasaoka

Papers

Historical Overview of the Establishment of Dietary Reference Intakes for Japanese

Association between the prevalence of hypertension and dairy consumption by housing type among survivors of the Great East Japan Earthquake.

The effects of changes in the meal providing system on emergency shelter menus following the Great East Japan Earthquake.

Frontiers in Disaster Nutrition: Evidence to Action.

Application of the Dietary Reference Intakes for Japanese to Government Food Guides and Dietary Guidelines