Is Staying at High Altitude Effective forImprovement of Metabolic Syndrome?

Kurobe City Hospital
Eisuke TAKAZAKURA, Shigeyoshi NAGASAKI

Metabolic Syndrome
・Abdominal obesity:
waist ≧ 34in.(male)≧ 36in.(female)・Hypertriglyceridemia:
TG ≧ 150mg/dl
・ HDL-C < 40mg/dl
・Hypertension:
systolic ≧ 130mmHg
diastolic ≧ 85mmHg

Coronary EventPeople lived in high altitude are mostly slender -in Nepal

SpO2 at sea level and high altitude（％）（％）
SpOSpO 22ObeseObese subjects＊＊ *＊ *98
9896969494929290908888Sea
Sea levellevel2nd3 rd2ndrd dayday
HighHi h altitudeltit dnergy expenditure at sea level andRestingRestingeenergy＊＊＊＊
high altitude
＊＊
＊＊
＊＊
＊＊

kcal/kg.day
kcal/kg.day

ns n=10＊＊：ｐ＜0.01＊＊：ｐ＜0.01＊：ｐ＜0.05＊：ｐ＜0.05
VS Sea Level
VSVS Sea
Sea Level
Level

24n=1122

＊＊
＊＊

＊＊
＊＊

2018SL

2nd3rd day
High altitude
ObeseSL

2nd 3 rd day
High altitude
Control

FFA,Total ketone and TG at sea level and high altitude
血中 FFA、 総ケトン体、TG の変化
TGTotalketones
総ケトン体FFAFFATGSL HA
平地
高所

ｐ＜ 0.001

mEq/l

n=111.0

ｐ＜ 0.01n=10217.1μmol/l

ns

mg/dl

200

200

141.1

0.810.8

ｐ＜ 0.010.6

ns

ns

0.52

100
0.38

0.4

105.4

100

84.4
67.3

0.28

108.8

75.5

57.0

0.2
00
肥満糖
Obese
尿病群

コントロールControl群

0Obese肥満糖
尿病群

コントロールControl群

肥満糖
Obese
尿病群

コントロールControl群

Changes of Blood Glucose (mouse)（mg/dl)200＊：p＜0.05
180＊＊:p＜0.01

160
140

＊＊

This slide shows the＊＊

＊＊

＊＊

2

34 days

120100
SLHA 1vs SeaLevel

HOMA-R at Sea Level and High Altitude(mouse)
Insulin（ng／ml）

HOMA-RP＜0.05p＜0.011.00

1280.50

40.000SL

HASL

HA

HOMA-R=Blood Glucose×IRI／405

In this study

Subjects and methods
SubjectsnAge(yr)

BMI

Fat%% Fat61149.7±12.0
60.6 ±7.4

23.7±1.528.8±4.7
23.5±8.4

Measurements
SpO2, HR，RR，REE
FBS, IRI,
S-Ketone bodies, FFA ,Noradrenalin
Leptin,Adiponectin

BW： Body weight

REE：Resting
REE：Resting energy expenditure

SL：Diagram of altitude
andand meteorology
meteorology

Mt.Fuji

3,776m（2,992ｍ）

Mt.Tateyama
3,000mMurodou

2,600 ｍ2,450m
2,200 ｍ（2280

Kurobe(SL)Humidity
Humidity

HeightHeight

Atmos press.

Temp(room)

Sea level

33 (m)

1,005 (hps)20.5 (℃)

（％）
（％）
45.9

HA:Murodou

2,450752

19.5

37.8

HA:Mt.Tateyama

3,000701

23.7

51.3

HA:Mt.Fuji

3,776635

20.8

51.5

Changes of SpO2 at Sea Level and High Altitude
(%)
100.0
＊＊
＊＊

＊＊

80.0

＊：p＜0.05＊＊:p＜0.01

vs Sea Level
60.0

Sea Level

MURODO

Mt.TATEYAMA

Mt.FUJI

Changes of HR・RR at Sea Level and High Altitude
Change of HR

Change of RR

(bpm)

(bpm)

20.0

100.0

＊

＊＊
＊＊

＊＊
＊

＊

70.0

15.0

40.0

10.0

Sea Level
Mt.TATEYAMAMURODO
Mt.FUJI

Sea Level

Mt.TATEYAMAMURODO
Mt.FUJI＊：p＜0.05＊＊:p＜0.01

vs Sea Level

Changes of REE at Sea Level and High Altitude(ml/kg.24h)
26.0

＊

＊
＊

24.0

22.0

＊：p＜0.05
20.0＊＊:p＜0.01

vs Sea Level
18.0
1

Sea Level

2

MURODO

3

OYAMA

4

Mt.FUJI

REE＝Resting Energy ExpenditureChanges of noradrenaline at Sea Level and High Altitude(pg/ml)1000800＊＊600

400＊：p＜0.05

200＊＊:p＜0.01

vs Sea Level

0Sea Level

MURODO

Mt.TATEYAMA

Mt.FUJI

Changes of FFA at Sea Level and High Altitude(mEq/l)0.600＊0.400＊：p＜0.05＊＊:p＜0.01

vs Sea Level
0.200

Sea Level

MURODOOYAMA

Mt.HUJI

Changes of S-Ketone bodies at Sea Level and High Altitude
（ｍM)

0.300

＊

＊

0.200

＊

0.100
＊：p＜0.05＊＊:p＜0.01

vs Sea Level

0.000

Sea Level

MURODO

Mt.TATEYAMA Mt.FUJI

Changes of HOMA-R at Sea Level and High Altitude
1.20＊0.80

0.40＊：p＜0.05＊＊:p＜0.01

vs Sea Level

0.00

Sea Level

MURODO

Mt.TATEYAMA

Mt.FUJI

HOMA-R＝FBS×IRI／405

A Possible Mechanism for the Effects on REE,Fat
and Glucose Metabolism by Hypoxia at High Altitude
Chemo-Hypothalamus

Resp.rate↑
NA↑

Hypoxia receptor M.O./Symp.N.C.↑
Methohormin
Exercise
Adiponectin
LeptinNA↑

β3AR？

Lipolysis↑

A M P-K↑
GlycogenAnerobic

UCP1↑

Heart rate↑

BMR↑

GlucoseBATACC ↓GLUT4Transloc. ↑pyruvate
Acetyl CoAFFAMalonyl CoA↓Glucose utiliz.↑

Glucose utiliz.↑
CPT1↑TCA-Cβ-Oxid.↑
ACC:acetyl coenzyme A carboxylase

AcCo

CPT1:carnitine palmitoyl transferase 1

Possible mechanism of reduction of fat in high altitude
PO22

Lipolysis and improvement of2insulin resistance may befacilitated owing to an increase of adrenergic activity andFFA

HSL activity

energy expenditure brought by hypoxia.
TGIn conclusion,
staying at high altitude may have beneficial

Reduction of fat＆ BW

effects on the subjects with metabolic syndrome.
Stopthethemetabolic
metabolicsyndrome
syndrome
StopThank you for your attention

Eisuke Takazakura,
Shigeyoshi Nagasaki
fromKurobe, Japan