基調講演 : こどもの肥満の現状 臨床の現場 から Clinical Aspects of Current Pediatric Obesity in Japan 日本大学医学部小児科客員教授 神奈川工科大学栄養生命科学科特任教授 岡田知雄 Tomoo Okada 第 4 回 食と生命のサイエンス・フォーラム 「子どもの肥満と食育 - 広がる健康対策の成果をたどる」

Contents Child Obesity in Japan and Western countries Relationship between Child obesity and the Environments Characteristics of Child obesity with Metabolic syndrome Abdominal Circumference and Fatty Acid Metabolism Low birth weight and catch-up Fat in DOHaD Effect of Cognitive Behavioral Therapy Very Low Calorie Diets for Morbid Obese Children

Prevalence % Source: IOTF 2004 Overweight children 7-11: Trends in the last three decades

年 Child obesity USA

Prevalence of Obesity in Junior High School Children 足立区中学生 (37 校）におけるやせ・肥満の出現率 2012 nprevalence Underweight girls % Severe obesity (total) % Obesity (total) 1, % nprevalence Underweight girls % Severe obesity (total) % Obesity (total) 1, % ％ Underweight mild moderate severe Obesity Boys (n=7,305) Girls (n=6,751) Total (n=14,056)

Outdoor playing and habitual exercise are important factors for prevention of Child Obesity( 肥満、脂肪肝 ) 4 th and 5 th Grade boys who moved from Gunma Pref. to Tokyo, they become obesity with fatty liver within only one year. 呑龍様 大光院 遊び： 外遊 び、木 登り 駆けっ こ、隠 れんぼ コンビニ、テレビゲー ム、遊び場無し、外遊 びなし。校庭開放？児 童館おかし？

仙田 満 Outdoor playing space in Yokohama わが国のこども達の遊び環境の変化 Outdoor playing space for children drastically decreased in 1960’s and 70’s.

日本小児科学会こどもの生活環境改善委員会（大国真彦ら）. 日本小児科学会雑誌 1997;99: Screen Time and Obesity in Children 子ども達がテレビ等視聴, ファミコン等で遊んでいる 実態と肥満との関係調査成績 1.Mean screen time :164 min/day 2.16:00 – 21:00 : 87 ％ of children watch TV. 3. Video watching time is longer in infants. 4. Video game time is longer in boys. 5. Screening time is positively correlated with percent overweight. Screen time (hr.) Percent overweight (%) Screen time (min.) 4:00-8:00 8:00-12:00 12:00-16:00 16:00-21:00 21:00-24:00 0:00-4:00 TV watching

Obese Children in Fukushima 福島民報 2012 年 12 月 25 日 Prevalence of obesity (%) Fukushima ’09’10‘12 The prevalence of obese children in Fukushima was the highest in all of Japan's 47 prefectures in National Average

平成 23 年度水産白書 肉の摂取量にはあまり変化がないが、 Decreasing intake of seafood appears every year Changes of intake seafood

Metabolic Syndrome in Children AdultsChildren 1) Abdominal circumference ≧ 85 cm （ Male ） ≧ 90 cm （ Female ） ≧ 80 cm （ Boys and Girls ） *: waist/height ratio ≧ 0.5 2) Serum lipids TG ≧ 150 mg/dl And ／ or HDLC < 40 mg/dl TG ≧ 120 mg/dl And ／ or HDLC < 40 mg/dl 3) Blood pressure SBP ≧ 130 mmHg And ／ or DBP ≧ 85 mmHg SBP ≧ 125 mmHg And ／ or DBP ≧ 70 mmHg 4) Fasting glucose ≧ 110 mg/dl ≧ 100 mg/dl Metabolic Syndrome : 1) and 、 2 components of 2), 3), 4) Diagnostic criteria of Metabolic Syndrome in Japan

Subclinical Atherosclerosis in Obese Children P < Subjects: 30 obese children Mean age; 10.7 years Mean percentage of overweight; 52.6 ％ 原 光彦 他：肥満研究 Vol.12(1), n.s. Non- Obese (n=41) Obese (n=30) × Liver Linea alba Pritonea Preperitoneal Fat Subcutaneous fat Abdominal ultrasonography

HOMA-R BoysGirls CRP BoysGirls D6D Activity BoysGirls * * D5D Activity BoysGirls * * * * * Desaturase Activities, HOMA-R and CRP Levels in Children with or without Abdominal Obesity. Saito E, Okada T, et al. Prostaglandins Leukot Essent Fatty Acids. 2013; 88: Children with abdominal obesity Children without abdominal obesity

Carbohydrates SCD; Stearoyl-CoA Desaturase Very Low-Density Lipoproteins Monounsaturated Fatty Acids

The relationship between DHA content and desaturase indices and variables Correlation Coefficientp value Body mass Index Waist/Height ratio Total Cholesterol (mg/dl) HDL-Cholsterol (mg/dl) Triglyceride (mg/dl) VLDL-Triglyceride (mg/dl) LDL-Cholesterol (mg/dl) Fasting Insulin Fasting Glucose HOMA-R SCD SCD D6D D5D obese children (27 male, 5 female) 12.0±2.6 years (mean ± SD) Relative body weight > 120% Docosahexaenoic acid content in plasma phospholipids and desaturase indices in obese children. Saito E, Okada T, et al.. J Atheroscler Thromb. 2011;18:

Study design Subjects:10 obese children （ 9 males, １ female ） Age:11 〜 16 years （ 12.9±1.5 ） Relative weight:137.0 〜 193.5% （ 52.0±17.3 ） Cod liver oil supplement:4 g/day for 12 weeks Results Cod Liver Oil Supplementation for Obese Children Fujita Y, Okada T et al. Obes Res & Clin Prac 2014, Articles in Press.

Effects of Fish Oil Supplementation on Markers of the Metabolic Syndrome Pedersen MH et al. J Pediatr 2010;157: Study design Subjects:78 boys Age:13 〜 15 years Body fat %:30.0 ± 9.0% (BMI = 22~25) Control study Fish oil (1.5 g n-3PUFA /day) for 16 weeks Vegetable oil for 16 weeks Conclusion VO group FO group SBP DBP HDLC Non-HDLC TG Insulin sensitivity VO group FO group SBP DBP HDLC Non-HDLC TG Insulin sensitivity

DHA induces beta-oxidation in adipocytes and the small intestine. Li JJ, Huang CJ, Xie D. Mol Nutr Food Res 2008;52: van Schothorst EM, et al.BMC Genomics. 2009;10:110. Flachs P, et al. Diabetologia. 2005;48: DHA inhibits adipocyte differentiation and induces apoptosis in 3T3- L1 preadipocytes. Kim HK, et al. J Nutr 2006;136: n-3 PUFAs markedly stimulate thermogenic activity in brawn adipose tissue. Oudart H, et al. Int J Obes Relat Metab Disord. 1997;21: Another possible mechanism, i.e. DHA suppression of SCD activity. Mechanisms for the anti-obesity effect of DHA, n-3 PUFAs

Developmental Origins of Health and Disease ： DOHaD David Barker proposed a hypothesis that undernutrition in utero permanently changes the body‘s structure, function and metabolism in ways that lead to atherosclerosis and insulin resistance in later life. Intrauterine undernutrition Obesity, Hypertension, Dyslipidemia, Insulin resistance Atherosclerotic Diseases 10 ％ 20 ％ ＜ 2.50 −2.95 ー 3.41 −3.86 − ＜ Birth Weight （ kg ） Prevalence of Syndrome X Barker DJ, et al. Diabetologia. 1993;36:62-7. Type 2 diabetes and hypertension have a common origin in sub-optimal development in utero, and that syndrome X should perhaps be re-named "the small-baby syndrome".

In LFD infants with catch-up growth in body weight, their subcutaneous fat is over-accumulated. Subcutaneous Fat Accumulation in Light-for-dates (LFD) Infants with Catch-up in Body Weight Skinfold Thickness (mm) Postconception period (day) Body Weight (g)

Gianni M, et al. Pediatr Res. 2007;72: % 100% 0% 35wk – term Birth/term – 1 mo mo 体脂肪増加率 (%) Subjects and Methods 49 late preterm infants (birth weight 2,496 ± 330 g, gestational age 35.2 ± 0.7 weeks) Body composition (day ５, term-equivalent age, corrected age １ mo., ３ mo. (PEA POD) Results Body Fat (%) Mean (SD) At birth, percentage of body fat in LPIs is lower than that in FTIs. At term-equivalent age, and corrected age 1 month, LPIs had greater percentage of body fat than FTIs. Rapid fat accumulation is demonstrated in LPIs during the first month of age (2.8- fold) Postnatal Catch-up Fat after Late Preterm Birth Percent increase in body fat

At birth r p Skinfold thickness VLDL-TG < At 1 month Skinfold thickness < VLDL-TG Cord bloodAt 1 month Correlation coefficients with lipoprotein lipase Yoshikawa K, Okada T, et al. Eur J Clin Nutr. 2010;64: Rapid subcutaneous fat accumulation may be induced by LPL activation in LFD infants. The Mechanism of Rapid Subcutaneous Fat Accumulation During First Month of Life

Adiposity Rebound Period Around 5yrs it begins generally Less than 5yrs if it start become later OB Adiposity rebound may be critical period to developing OB Dietz W. Critical periods in childhood for the development of obesity Am.J.Clin.Nutr (1994)59;

Daily-life Checking Sheet チェックした日 /////// 総計総計 /////// 総計総計 早起きをする（ : ） 朝ごはんを食べる 給食の時おかわりしな い 夜食はたべない ジュースを飲まない おやつの量を守る 体を動かす テレビやゲームは 2 時間 以内 家の手伝いをする 早く寝る（ : ） 合計 都立広尾病院小児生活習慣病外来 Cognitive Behavioral Therapy Including Self-monitoring

Two Cases of Severe Pediatric Obesity Case 1. S.S. 2y. 6m. Boy Case 2. N.K. 15y. 2m. Boy Height (cm) Weight (kg) SD +1SD Mean -1SD -2SD +2SD +1SD Mean -1SD -2SD SD +1SD Mean -1SD -2SD +2SD +1SD Mean -1SD -2SD Height (cm) Weight (kg)

内田則彦、朝山光太郎、他：日児誌 104(4), , 2000 のデータから作図 Cognitive Behavioral Therapy for Obese Children Improved Not improved Boys Girls Total Subjects and Methods 50 obese children (mean age 9 y.o., mean relative weight 147.6%) After the cognitive behavioral therapy using the daily-life checking sheet for 200 days, improved: Δ relative weight -30%

Very Low Calorie Diets for Morbid Obese Children Mean±SD n15 Age （ year ） 15.9±4.9 Sex10M/5F Height (cm)162.5±10.2 Weight (kg)92.8±22.0 Percent of Overweight (%)74.3±31.2 Subjects and Methods 165 kcal/meal (Breakfast) for 2 months 163.6± ± ±28.0 Percent of Overweight Results

Summary Lifestyle interventions are effective for mild obese children, especially when initiated at a young age. However, in cases of severe morbid obesity, it is difficult to treat successfully. Therefore, efforts should be focused on the prevention of obesity from early childhood.