Michel P. HERMANS

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Energy Storage in the Animal KingdomCommonalities
with Human Metabolic Syndrome

• Michel P. HERMANS
• M.D. Ph.D. Dip.Nat.Sci. Dip.Earth.Sci.
• Dip.Geog.Env. P.G.Cert. (Soc.Sci.) (Open)
• Service dEndocrinologie et Nutrition
• Cliniques universitaires UCL Saint Luc

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• Lipogenesis and Fat oxidation in humans
• Insulin signalling, SREBP and lipogenesis
• Comparative DNL in vertebrates
• Shifts in fuel utilization
• Seasonal hibernation
• Seasonal migratory birds
• Cost of fat in avians
• Life-cycle history in insects
• Fat Body in insects

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LCACoAs are either esterified or oxidised
OCO
IMCL
VLDL
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Acetyl-CoA activated acetic acid
Acetyl-
Coenzyme A
AMPK
ACC1 / 2
MCD
insulin
glucagon
Malonyl-
Coenzyme A
FAS
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Lipogenesis
FAS
CPT-I
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glucose
citrate
acetyl-CoA
ACC
AMPK
FAS
malonyl-CoA
DAG
LCFACoA
TG
GPAT
VLDL
CPT-I
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leptin
adiponectin
IS drugs
acetyl-CoA
ACC
AMPK
FAS
malonyl-CoA
DAG
LCFACoA
TG
GPAT
MCD
Muscle TG
CPT-I
VLDL-TG
oxidation
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glucose
citrate
FFAs
acetyl-CoA
ACC
AMPK
IMCL
FAS
malonyl-CoA
DAG
CERAMIDES
LCFACoA
TG
GPAT
MCD
CPT-I
VLDL
oxidation
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LCACoA pool expansion upstream of the mitochondria

• Number, size, function, combination
• Mutations frequent acquired or genetic
• Mt DNA / or Nucl DNA
• Aging, drugs
• Oxidative stress
• Obesity decreased size
• Young Off T2DM

PGC-1 alpha
PGC-1 beta
Hereditary IR IMGU
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Insulin receptor IR
Insulin resistance vs. hyperinsulinemia
PPAR-?
PT1B
PKC?
SHIP
JNK
PTEN
PKC
PDK1
GLUT4
translocation
glycolysis
PKC ?,?
gluco-oxidation
PKB???/Akt123
glycogenosynthesis
? gluconeogenesis
GPAT
protein synthesis
SCD1
mitogenesis
PDK2
growth
? apoptosis
FAS
PDE-3B
? lipolysis (? in ?)
ACC
SRE
SREBP-1c
lipogenesis
er..G..n SREBP-1c
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Shifts in Fuel Utilization in Hibernation
INSULIN
T2DM
PKB???/Akt123
starvation
SREBP-1c
lipogenesis
Lipolysis
FFA oxidation
CH oxidation
PPAR-?
PPAR-?
UCP3
?-oxid
FFAs
FFAs
PDK-4
PDK-4
FFA transport
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Adipose energy stores, physical work, and the
metabolic syndrome lessons from
hummingbirds James L Hargrove Nutr J. 2005 4 36

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• Migratory energetics in Ruby-Throated
  Hummingbirds
• Adult 3-4 g 21 fat (non-migrating period x2
  prior to migration)
• Nectar 38 CH (sucrose) CH as flight fuel in
  non-migratory period
• FPG 17 mM PPPG 42 mM
• Feed every 15-20 min.
• Seasonal weight gain 1-2 g
• Nocturnal torpor FFA during the night
• Flight O2 consumption 1000 vs. humans
• HR in flight 1000/min BR 250/min
• Switch to FFA for migratory flight glycemia will
  allow a few min. flight

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• Migratory energetics in Ruby-Throated
  Hummingbirds
• 1-2 g fat allows for crossing the Gulf of Mexico
  without food or drink
• Flying speed 25-50mph
• Hovering and manoeuvrability
• Not polyuric reabsorption of glucose no
  elevation in HbA1c (no glucotoxicity)
• IR / hyper-Ins but no ectopically unfavourable
  fat (pericardium)
• Theoretical estimates of glycogen storage would
  represent 10 g (not enough lift)
• Highly aerobic and acrobatic lifestyle

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• Ecological Costs of Avian Fat
• Benefits
• Body insulation
• Mechanical support
• Protection
• Buoyancy
• Sexual traits social signals
• Energy store
• flapping/hovering flight most energetically-demand
  ing
• migration
• inclement wheather
• stochastic foraging success

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• Ecological Costs of Avian Fat
• Mass-dependent Costs (1)
• Metabolic expenditure
• Biomechanical power requirements
• Fat-dependent resting metabolism
• Fat storage expenditure
• Predation risk
• Take-off ability escape from terrestrial
  predators
• Flight performance
• Attractivity to predators
• Perceived risk of feeding behaviour
• Higher fat in island subspecies

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• Ecological Costs of Avian Fat
• Mass-dependent Costs (2)
• Injury
• In-flight collisions
• Landing crashes
• Birds momentum and severity of injury
• Decreased choice of landing surfaces (branches
  twigs)
• Pre-landing manoeuvers more complex
• Foraging
• Decreased ability (arboreal /or hovering)
• Need for corrective feeding/foraging behaviours
• Pathological
• Reproductive Life-History Theory

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Insects Fat Body ?intermediate metabolism
?carbohydrate storage organ ?adipose tissue
?innate immunity
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AKH-HTH
TAG
TAG
TAG lipase
LTP
DAG
DAG
LpL
HEXAMERINS
FFA
apoLp-III
GLYCOGEN
TREHALOSE
PROLINE
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Libellula pulchella
IR
P38 MAPK
GLUCOSE
TAG
TAG
DAG
DAG
FFA
IR
Gregarines (Apicomplexa)
GLYCOGEN
TREHALOSE
non-invasive