ㄽ ᩥ ෆ ᐜ せ ᪨Effects of long-term childhood exercise anddetraining on lipid accumulation in metabolic-relatedorgans௦ㅰ㛵㐃⮚ჾࡢ⬡㉁⵳✚࡟ᑐࡍࡿᑠඣᮇࡢ㛗ᮇ㐠ືຠᯝ࡜ࢺ࣮ࣞࢽࣥࢢゎ㝖ࡢᙳ㡪 PLoS ONE, 2022, 17(6):e0270330.

୺ᣦᑟᩍဨ㸸ᾆᕝᑗᩍᤵ㸦་⣔⛉Ꮫ◊✲⛉㐠ືჾᶵ⬟་⛉Ꮫ㸧๪ᣦᑟᩍဨ㸸℈⏣Ὀఙᩍᤵ㸦་⣔⛉Ꮫ◊✲⛉⏕యᶵ⬟ゎᯒไᚚ⛉Ꮫ㸧๪ᣦᑟᩍဨ㸸ᑎᒣ㝯ྖᩍᤵ
㸦་⣔⛉Ꮫ◊✲⛉㢡㢦㠃ゎ๗Ꮫ㸧NGUYEN SON TIEN㸦་⣔⛉Ꮫ◊✲⛉⥲ྜ೺ᗣ⛉Ꮫᑓᨷ㸧

AbstractChildhood obesity is globally on the rise and carried over to adulthood. Obese children have a higher riskof developing metabolic disorders later in life. Interventions for obesity include diet, exercise, and medicaltreatments, and those are proven effective on preventing and treating. However especially in exercise, obese
children tend to have trouble adhering to a continual exercise program. Therefore, discontinuation ofexercise could induce a detraining effect, which may negatively impact children’s metabolic health. In
obese adults, after cessation of exercise, lipid accumulations in the whole body appear to partially orcompletely attenuate the effectiveness of the previous exercise. Lipid accumulation during the detraining
period occurs in the main lipid supply organs, such as the intra-abdominal white adipose tissue (WAT),
brown adipose tissue (BAT), and liver. Moreover, lipid accumulation in organs increases insulin resistance,
which is similar to a vicious cycle. However, information regarding lipid accumulation in children withobesity undergoing detraining is limited. Therefore, we conducted this study with the aim of evaluating theeffect of early long-term regular exercise and detraining on the prevention of childhood obesity through fat
accumulations in metabolic-related organs.
Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an obesity model characterized by hyperphagia dueto the loss of cholecystokinin receptor-1 in the dorsomedial hypothalamus, leading to decreased satiety.
The natural progression of obesity and obesity-related metabolic complications in OLETF rats reflects
human childhood obesity, leading to metabolic health problems in adulthood. Therefore, in our study, fourweek-old male OLETF and Long-Evans Tokushima Otsuka rats were employed as obese and non-obese
control groups. OLETF rats were assigned to sedentary and exercise groups. The exercise group performed
wheel running from 4 to 12 week-old (i.e, childhood period) and detraining from 12 to 20 week-old (i.e,transition period from childhood to adulthood).
At 12-week-old immediately after the exercise period, regular exercise completely inhibited hyperphagia,
obesity, enlarged pancreatic islets, lipid accumulation and lobular inflammation in the liver, hypertrophied
adipocytes in the WAT, and BAT whitening in OLETF rats. In addition, exercise attenuated the decrease in
the ratio of muscle wet weight to body weight associated with obesity. Decreased food consumption wasmaintained during the detraining period, which inhibited obesity and diabetes at 20-week-old after thedetraining period. Histologically, childhood exercise inhibited the enlargement of pancreatic islets after thedetraining period. In addition, inhibition of lipid accumulation was completely maintained in the WAT andBAT after the detraining period. However, the effectiveness was only partially successful in lipid
accumulation and inflammation in the liver. The ratio of muscle wet weight to body weight was maintained
after detraining.
In conclusion, early long-term regular exercise effectively prevents obesity and diabetes in childhood, andits effectiveness can be tracked later in life. The present study suggests the importance of exercise duringchildhood and adolescence to inhibit hyperphagia-induced lipid accumulation in metabolic-related organs
in adulthood despite exercise cessation.

ᑠඣ⫧‶ࡣୡ⏺ⓗ࡟ቑຍࡋ࡚࠾ࡾࠊᡂேᮇ࡟ࡑࡢᙳ㡪ࡀᣢࡕ㉺ࡉࢀ࡚࠸ࡲࡍࠋ⫧‶ࡢᏊ౪ࡣࠊᚋᖺ࡟௦ㅰ㞀ᐖࢆⓎ⑕ࡍࡿࣜࢫࢡࡀ㧗ࡃ࡞ࡾࡲࡍࠋ⫧‶࡬ࡢ௓ධ࡟ࡣࠊ㣗஦⒪ἲࠊ㐠ືࠊ࠾ࡼࡧ་Ꮫⓗ἞⒪ࡀྵࡲࢀࠊࡑࢀࡽࡣண㜵࠾ࡼࡧ἞⒪࡟ຠᯝࢆࡶࡓࡽࡍࡇ࡜ࡀド᫂ࡉࢀ࡚࠸ࡲࡍࠋࡋ࠿ࡋࠊ≉࡟㐠ື࡛ࡣࠊ⫧‶ࡢᏊ౪ࡀ⥅⥆ⓗ࡞㐠ືࣉࣟࢢ࣒ࣛࢆ㡰Ᏺࡍࡿࡢ࡟ⱞປࡍࡿഴྥࡀ࠶ࡾࡲࡍࠋࡋࡓࡀࡗ࡚ࠊ㐠ືࢆ୰Ṇࡍࡿ࡜ࠊ⬺カ⦎ຠᯝ࡜ࡋ࡚Ꮚ౪ࡢ௦ㅰࡢ೺ᗣ㠃࡟ᝏᙳ㡪ࢆࡶࡓࡽࡋࡲࡍࠋ
⫧‶ࡢᡂே࡛ࡣࠊ㐠ືࢆࡸࡵࡓᚋࠊ㌟య࡟⬡⫫ࡀ㒊ศⓗ࠶ࡿ࠸ࡣ඲య࡟⵳✚ࡍࡿ࡜ࠊ௨๓ࡢ㐠ືຠᯝࡀῶᙅࡋ࡚ࡋࡲ࠸ࡲࡍࠋ⬺カ⦎ᮇ㛫୰ࡢ⬡㉁⵳✚ࡣࠊ⭡⭍ෆࡢⓑⰍ⬡⫫⤌⧊㸦WAT㸧ࠊ〓Ⰽ⬡⫫⤌⧊㸦BAT㸧ࠊ⫢⮚࡞࡝୺せ࡞⬡㉁౪⤥ჾᐁ࡛Ⓨ⏕ࡋࡲࡍࠋࡉࡽ࡟ࠊ⮚ჾ࡟⬡㉁ࡀ⵳✚ࡍࡿ࡜࢖ࣥࢫࣜࣥ᢬ᢠᛶࡀ㧗ࡲࡾࠊᝏᚠ⎔ࢆࡶࡓࡽࡋࡲࡍࠋࡋ࠿ࡋ࡞ࡀࡽࠊ⬺カ⦎࡟ࡼࡿ⫧‶ࡢᏊ౪࡟ࡳࡽࢀࡿ⬡㉁⵳✚࡟ࡘ࠸࡚ࡢ᝟ሗࡣ㝈ࡽࢀ࡚࠸ࡲࡍࠋࡑࡢࡓࡵࠊᡃࠎࡣࠊ᪩ᮇࡢ㛗ᮇᐃᮇ㐠ື࡜⬺カ⦎ࡢຠᯝࡀࠊ௦ㅰ㛵㐃⮚ჾ࡬ࡢ⬡⫫⵳✚࡟ࡼࡿᑠඣ⫧‶ࡢண㜵࡟ࡶࡓࡽࡍᙳ㡪ࢆ᳨ドࡍࡿࡇ࡜ࢆ┠ⓗ࡜ࡋ࡚◊✲ࢆᐇ᪋ࡋࡲࡋࡓࠋ
Otsuka Long-Evans Tokushima Fatty㸦OLETF㸧ࣛࢵࢺࡣࠊ⫼ෆഃどᗋୗ㒊ࡢࢥࣞࢩࢫࢺ࢟ࢽ
ࣥཷᐜయ-1 Ḟᦆ࡟ࡼࡿ‶⭡ឤపୗ࡟ࡼࡗ࡚㐣㣗⑕ࡀࡶࡓࡽࡉࢀࡿ≉ᚩࢆ᭷ࡍࡿ⫧‶ࣔࢹࣝື≀࡛ࡍࠋ OLETF ࣛࢵࢺ࡟࠾ࡅࡿ⫧‶࠾ࡼࡧ⫧‶㛵㐃ࡢ௦ㅰᛶྜే⑕ࡢ⮬↛㐍⾜ࡣࠊࣄࢺࡢᑠඣ⫧‶ࢆ཯ᫎࡋ࡚࠾ࡾࠊᡂேᮇࡢ௦ㅰࡢ೺ᗣ㠃࡟ၥ㢟࡜࡞ࡾࡲࡍࠋࡋࡓࡀࡗ࡚ࠊᡃࠎࡢ◊✲࡛ࡣࠊ㛤ጞ᫬ 4 㐌㱋ࡢ㞝 OLETF ࠾ࡼࡧ Long-Evans Tokushima Otsuka ࣛࢵࢺࢆ⫧‶࠾ࡼࡧ㠀⫧‶ࡢᑐ↷⩌࡜ࡋࡲࡋࡓࠋ OLETF ࣛࢵࢺࡣࠊ㐠ື⩌࡜㠀㐠ື⩌࡟ศࡅࡲࡋࡓࠋ㐠ືࢢ࣮ࣝࣉࡣࠊ4ࠥ12 㐌㱋㸦ᑠඣᮇ࡟┦ᙜ㸧࠿ࡽ㍯㌴㐠ືࢆ⾜࠸ࠊ12ࠥ20 㐌㱋㸦ᡂேᮇ࡬ࡢ⛣⾜ᮇ࡟┦ᙜ㸧࡟⬺カ⦎ࢆタᐃࡋࡲࡋࡓࠋ
㐠ືᮇ㛫┤ᚋࡢ 12 㐌㱋࡛ࡣࠊᐃᮇⓗ࡞㐠ື࡟ࡼࡾࠊ㐣㣗⑕ࠊ⫧‶ࠊ⮅⮚ࡢ⫧኱ࠊ⫢⮚ࡢ⬡㉁⵳
✚࡜⫢ᑠⴥࡢ⅖⑕ࠊWAT ࡢ⫧኱ࡋࡓ⬡⫫⣽⬊ࠊOLETF ࣛࢵࢺࡢ BAT ࡢⓑⰍ໬ࡀ᏶඲࡟ᢚไࡉࢀࡲࡋࡓࠋࡉࡽ࡟ࠊ㐠ືࡣࠊ⫧‶࡟㛵㐃ࡍࡿయ㔜࡟ᑐࡍࡿ➽⫗ࡢ‵㔜㔞ẚ⋡ࡢῶᑡࢆᙅࡵࡲࡋࡓࠋ⬺カ⦎ᮇ㛫୰ࡶᦤ㣵㔞ࡢῶᑡࡀ⥔ᣢࡉࢀࠊࡑࢀ࡟ࡼࡾ⬺カ⦎ᮇ㛫ᚋࡢ 20 㐌㱋࡛ࡶ⫧‶࡜⢾ᒀ⑓ࡀᢚไࡉࢀࡲࡋࡓࠋ⤌⧊Ꮫⓗ࡟ࠊᑠඣᮇࡢ㐠ືࡣࠊ⬺カ⦎ᮇ㛫ᚋࡢ⮅⮚ᣑ኱ࢆᢚไࡋࡲࡋࡓࠋࡉࡽ࡟ࠊ⬡㉁⵳✚ࡢᢚไࡣࠊ⬺カ⦎ᮇ㛫ᚋࠊWAT ࠾ࡼࡧ BAT ࡟࠾࠸࡚᏶඲࡟⥔ᣢࡉࢀࡲࡋࡓࠋࡋ࠿ࡋࠊ⫢⮚࡛ࡢ⬡㉁⵳✚࡜⅖⑕࡛ࡣࠊຠᯝࡣ㒊ศⓗ࡟ࡳࡽࢀࡲࡋࡓࠋయ㔜࡟ᑐࡍࡿ➽⫗ࡢ‵㔜㔞ẚ⋡ࡣࠊ⬺カ⦎ᚋࡶ⥔ᣢࡉࢀࡲࡋࡓࠋ⤖ㄽ࡜ࡋ࡚ࠊ᪩ᮇࡢ㛗ᮇᐃᮇ㐠ືࡣࠊᑠඣᮇࡢ⫧‶࡜⢾ᒀ⑓ࢆຠᯝⓗ࡟ண㜵ࡋࠊࡑࡢ᭷ຠᛶࡣࡑࡢᚋ࡟ࡶ☜ㄆࡍࡿࡇ࡜ࡀ࡛ࡁࡲࡋࡓࠋᮏ◊✲ࡣࠊᡂேᮇࡢ௦ㅰ㛵㐃ჾᐁ࡟࠾ࡅࡿ㐣㣗⑕࡟ࡼࡿ⬡㉁⵳✚ࢆ㜼ᐖࡍࡿࡓࡵ࡟ࠊࡓ࡜࠼㐠ືࢆࡸࡵࡿࡇ࡜࡟࡞ࡗ࡚ࡶᑠඣᮇ࠾ࡼࡧ㟷ᖺᮇ࡟࠾ࡅࡿ㐠ືᐇ᪋ࡢ㔜せᛶࢆ♧၀ࡋ࡚࠸ࡲࡍࠋ