Effect of ,0-Hydroxybutyrate on Whole-Body Leucine Kinetics and Fractional
Mixed Skeletal Muscle Protein Synthesis in Humans
K. Sreekumaran Nair, Stephen L. Welle, David Halliday,* and Robert G. Campbell
Department ofMedicine, University ofRochester School ofMedicine and Dentistry, Rochester NY 14603;
and the *Nutrition Group, Clinical Research Centre, Harrow HA] 3UJ, United Kingdom
Abstract
Because intravenous infusion of 0-hydroxybutyrate (8-OHB)
has been reported to decrease urinary nitrogen excretion, we
investigated in vivo metabolism of leucine, an essential amino
acid, using L-11-'3Cjleucine as a tracer during t9-OHB infusion.
Leucine flux during ,B-OHB infusion did not differ from leucine
flux during normal saline infusion in nine normal subjects,
whereas leucine oxidation decreased 1841% (mean = 30%)
from 18.1±1.1 pmol * kg-' * h-1 (P < 0.01), and incorporation
of leucine into skeletal muscle protein increased 5-17% (mean
= 10%) from 0.048 + 0.003%/h (P < 0.02). Since blood pH
during jt-OHB infusion was higher than the pH during saline
infusion, we performed separate experiments to study the effect
of increased blood pH on leucine kinetics by infusing sodium
bicarbonate intravenously. Blood pH during sodium bicarbonate
infusion was similar to that observed during the
,B-OHB infusion, but bicarbonate infusion had no effect on
leucine flux or leucine oxidation. We conclude that #-OHB
decreases leucine oxidation and promotes protein synthesis in
human beings.

Altra cosa: l'aumento di beta-idrossibutirrato, un corpo chetonico, che si ha durante la restrizione glicidica tende a preservare l'ossidazione della leucina (amino essenziale nel messoggio di disponibilità proteica). I + alti livelli di BHB li abbiamo in ketosi, ma il problema è che una dieta alta in grassi fa si che la ketogenesi venga attivata dai grassi esogeni, durante il digiuno, invece, la sintesi di KB (ketone body) avviene dai soli grassi endogeni e quindi avremo un vero e proprio smantellamento delle riserve adipose. Essere in ketosi durante il digiuno vuole dire ossidare solo i propri grassi.
Il problema è che + un soggetto è magro + il suo corpo è restio a rilasciare FFA dal tessuto adiposo, questo per vari adattamenti ormonali che inibiscono la lipolisi (come ha spiegato Duch).
Quindi diventa indispensabile aumentare intensità e tempistica dei refeeding con il diminuire della BF.

Regulation of Energy Balance and Carbohydrate/Lipid
Metabolism
Peter J. Havel
Hormones produced by adipose tissue play a critical role
in the regulation of energy intake, energy expenditure,
and lipid and carbohydrate metabolism. This review will
address the biology, actions, and regulation of three adipocyte
hormones—leptin, acylation stimulating protein
(ASP), and adiponectin—with an emphasis on the most
recent literature. The main biological role of leptin appears
to be adaptation to reduced energy availability
rather than prevention of obesity. In addition to the
well-known consequences of absolute leptin deficiency,
subjects with heterozygous leptin gene mutations have
low circulating leptin levels and increased body adiposity.
Leptin treatment dramatically improves metabolic abnormalities
(insulin resistance and hyperlipidemia) in patients
with relative leptin deficiency due to lipoatrophy.
Leptin production is primarily regulated by insulin-induced
changes of adipocyte metabolism. Dietary fat and
fructose, which do not increase insulin secretion, lead to
reduced leptin production, suggesting a mechanism for
high-fat/high-sugar diets to increase energy intake and
weight gain. ASP increases the efficiency of triacylglycerol
synthesis in adipocytes leading to enhanced postprandial
lipid clearance. In mice, ASP deficiency results in reduced
body fat, obesity resistance, and improved insulin sensitivity.
Adiponectin production is stimulated by thiazolidinedione
agonists of peroxisome proliferator-activated
receptor- and may contribute to increased insulin sensitivity.
Adiponectin and leptin cotreatment normalizes insulin
action in lipoatrophic insulin-resistant animals.
These effects may be mediated by AMP kinase–induced fat
oxidation, leading to reduced intramyocellular and liver
triglyceride content. The production of all three hormones
is influenced by nutritional status. These hormones, the
pathways controlling their production, and their receptors
are promising targets for managing obesity, hyperlipidemia,
and insulin resistance. Diabetes 53 (Suppl. 1):
S143–S151, 2004


Poi guarda questo studio. L'overfeeding a base di CHO (50% surplus) aumenta la DNL (de novo lipogenesi) di soli 5gr al giorno. Ed i soggetti dello studio nn conducevano alcuna attività fisica.

Short-Term Alterations in Carbohydrate Energy Intake in Humans
Striking Effects on Hepatic Glucose Production, De Novo Lipogenesis, Lipolysis, and Whole-Body
Fuel Selection
Jean-Marc Schwarz,* Richard A. Neese,*" Scott Tumer,* Doris Dare,* and Marc K. Hellerstein**
*Department of Nutritional Sciences, University of California, Berkeley, California 94720-3104; and tDivision of Endocrinology and
Metabolism, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California 94110
Abstract
Short-term alterations in dietary carbohydrate (CHO) energy
are known to alter whole-body fuel selection in humans,
but the metabolic mechanisms remain unknown. We used
stable isotope-mass spectrometric methods with indirect calorimetry
in normal subjects to quantify the metabolic response
to six dietary phases (5 d each), ranging from 50%
surplus CHO (+50% CHO) to 50% deficient CHO (-50%
CHO), and 50% surplus fat (+50% fat). Fasting hepatic
glucose production (HGP) varied by > 40% from deficient
to surplus CHO diets (1.78+0.08 vs 2.43+0.09 mg/kg per
min, P < 0.01). Increased HGP on surplus CHO occurred
despite significantly higher serum insulin concentrations.
Lipolysis correlated inversely with CHO intake as did the
proportion of whole-body lipolytic flux oxidized. Fractional
de novo hepatic lipogenesis (DNL) increased more than 10-
fold on surplus CHO and was unmeasurable on deficient
CHO diets; thus, the preceding 5-d CHO intake could be
inferred from DNL. Nevertheless, absolute hepatic DNL accounted
for < 5 g fatty acids synthesized per day even on
+50% CHO. Whole-body CHO oxidation increased sixfold
and fat oxidation decreased > 90% on surplus CHO diets.
CHO oxidation was highly correlated with HGP (r2 = 0.60).
HGP could account for 85% of fasting CHO oxidation on
+25% CHO and 67% on +50% CHO diets. Some oxidation
of intracellular CHO stores was therefore also occurring.
+50% fat diet had no effects on HGP, DNL, or fuel selection.
We conclude that altered CHO intake alters HGP specifically
and in a dose-dependent manner, that HGP may
mediate the effects of CHO on whole-body fuel selection
both by providing substrate and by altering serum insulin
concentrations, that altered lipolysis and tissue oxidation
efficiency contribute to changes in fat oxidation, and that
surplus CHO is not substantially converted by the liver to
fat as it spares fat oxidation, but that fractional DNL may
nevertheless be a qualitative marker of recent CHO intake.
(J. Clin. Invest. 1995. 96:2735-2743.)


Inoltre l'ipernutrizione a base di carbo aumenta di circa 11% il RMR e quindi la termogenesi

Stimulation of Thermogenesis by
Carbohydrate Overfeeding
EVIDENCE AGAINST SYMPATHETIC NERVOUS SYSTEM MEDIATION
STEPHEN WELLE and ROBERT G. CAMPBELL, Endocrine-Metabolism Unit, Monroe
Community Hospital, Department of Medicine, University of Rochester
School of Medicine and Dentistry, Rochester, New York 14603
A B S T R A C T Daily carbohydrate intake of seven men
with normal weight was limited to 220-265 g/d for
6 d and then increased to 620-770 g/d for 20 d, while
intake of protein, fat, and sodium remained constant.
Carbohydrate overfeeding increased body weight by
4.8%, basal oxygen consumption (Vo2) by 7.4%, BMR
by 11.5%, and serum triiodothyronine levels by 32%.
Overfeeding did not affect the thermic effect of a standard
meal. Intravenous propranolol reduced the
thermic effect of a meal by 22% during the base-line
feeding period, and by 13% during carbohydrate overfeeding,
but did not affect preprandial Vo2. Overfeeding
attenuated the rise in plasma glucose and FFA
levels induced by infusion of norepinephrine, but had
no effect on the increase in Vo2 induced by norepinephrine.
Overfeeding did not alter 24-h urinary excretion
of vanillylmandelic acid, supine plasma catecholamine
levels (pre- and postprandial), blood pressure,
or plasma renin activity, but increased peak
standing plasma norepinephrine levels by 45% and
resting pulse rate by 9%. Even though short-term carbohydrate
overfeeding may produce modest stimulation
of sympathetic nervous system activity in man,
the increase in thermogenesis induced by such overfeeding
is neither suppressed by beta adrenergic blockade
nor accompanied by an increased sensitivity to the
thermogenic effects of norepinephrine. These data do
not support an important role for the sympathetic nervous
system in mediating the thermogenic response to
carbohydrate overfeeding.

è anche vero che il fasting tende ad abbassare la sensibilità nsulinica.
Ma questo problema nn rigurda gli atleti. L'allenamento migliora la sensibilità insulinica upregolando gli IR (recettori insulinici) ed stimolando degli8 adattamenti che fanno si che la membrana cellulare diventi maggiormente permeabili al glucosio e stimolando l'aumento dei trasportatori si glusoio GLUT-4 sulle membrane cellulari


Differential regulation of metabolic genes in skeletal muscle during starvation and refeeding in humans


Littlewood, Ian Macdonald and Andrew Bennett
Kostas Tsintzas, Kirsty Jewell, Mo Kamran, David Laithwaite, Tantip Boonsong, Julie



Abstract
This study investigated the molecular alterations underlying the physiological adaptations to starvation and refeeding in human skeletal muscle. 48 h starvation reduced whole body insulin sensitivity by 42% and produced marked changes in expression of key carbohydrate (CHO) regulatory genes and proteins: SREBP1c and hexokinase II (HKII) were downregulated 2.5- and 5-fold respectively whereas the pyruvate dexydrogenase kinase 4 (PDK4) was upregulated 4-fold. These responses were not dependent on the phosphorylation status of Akt and FOXO1. On the other hand, starvation and the concomitant increase in circulating free fatty acids did not upregulate the expression of transcription factors and genes involved in fat metabolism. 24 h refeeding with a CHO-rich diet completely reversed the changes in PDK4, HKII and SREBP1c expression in human skeletal muscle but failed to fully restore whole body insulin sensitivity. Thus, during starvation in healthy humans, unlike rodents, regulation of fat metabolism does not require an adaptive response at transcriptional level, but adaptive changes in gene expression are required to switch off oxidative glucose disposal. Lack of effect on key proteins in insulin-signalling pathway may indicate that changes in intracellular substrate availability/flux may be responsible for these adaptive changes in glucose metabolism. This may represent an important aspect of the molecular basis of the development of insulin resistance in metabolic conditions characterised by energy restriction.



Adesso unisci il tutto in un piano dietetico composto da 2 estremi:
1)fortissima restrizione calorica o meglio "digiuno controllato" poichè si assumono solo protidi (2gr/kg LBM) e grassi essenziali (6gr O3 da pesce o 10gr olio di lino) potratta per 4 o 5 gg dove ciò che ossidi sono solo i tuoi grassi
2)ricarica intensa di 12 o 24 ore a base di CHO in cui vengono ricaricate solo le riserve muscolari di glicogeno con una DNL di meno di 5gr al giorno (irrisoria)

penso che si possano ottenere migliori e + rapidi risultati rispetto ad una dieta meno restrittiva


Poi questo, che mostra come la sottoalimentazione aumenti il gene Sirt1. Il quale inibisce i PPAR-gamma, recettori deputati alla lipogenesi ed alla differenziazione dei pre adipociti in adipociti. Inoltre fungendo da PPAR-gamma antagonista, il Sirt1 aumenta la lipolisi

Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.

Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L.

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Calorie restriction extends lifespan in organisms ranging from yeast to mammals. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction. Here we show that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal Sirt1 protein binds to and represses genes controlled by the fat regulator PPAR-gamma (peroxisome proliferator-activated receptor-gamma), including genes mediating fat storage. Sirt1 represses PPAR-gamma by docking with its cofactors NCoR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptors). Mobilization of fatty acids from white adipocytes upon fasting is compromised in Sirt1+/- mice. Repression of PPAR-gamma by Sirt1 is also evident in 3T3-L1 adipocytes, where overexpression of Sirt1 attenuates adipogenesis, and RNA interference of Sirt1 enhances it. In differentiated fat cells, upregulation of Sirt1 triggers lipolysis and loss of fat. As a reduction in fat is sufficient to extend murine lifespan, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals.

Naturalmente la ricerca è ancora lunga

questo il link: http://www.fituncensored.com/forums/...ead.php?t=6932