energy balance--- what should we teach our students? energy balance--- what should the textbooks...
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Energy Balance--- What should we teach our students?
Energy Balance--- What should the textbooks teach our students?
HAPS 17th Annual Conference
Itzick Vatnick ---Widener UniversityURL: htpp://science.widener.edu/~vatnick email [email protected]
Energy Balance
Body weight
in out
Negative Energy Balance
Body weight
in
out
Positive Energy Balance
Body weight
in
out
Energy in
How do we measure energy in foods?
home.wanadoo.nl/fox-1/ farside/eating.gif
Editorial comment:
No more Larson?
kilocalorie (kcal):
eg. a half cup of peanut butter contains ~750 kcal; or enough energy to heat 750 L of water by 1°C !!
SI unit is the kilojoule (kJ): kcal x 4.184
energy content of food measured by direct calorimetry
complete combustion of known amount of food in a sealed, insulated container measure increase in temperature of surrounding water jacket known as bomb calorimetry
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Gross energy content of macronutrients, determined by combustion
carbohydrate: 4.2 kcal per gram
fat: 9.4 kcal per gram (due to greater relative hydrogen content)
protein: 5.6 kcal per gram
Actual (net) energy content of macronutrients (called Atwater General Factors)
loss of H atoms as urea (ie. loss of protein energy)
coefficient of digestibility
usually > 90%, some variability
reduced by dietary fiber
generally NOT different between lean and obese individuals !!
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Macronutrient Atwater General Factor
Carbohydrate 4 kcal per gram
Fat 9 kcal per gram
Protein 4 kcal per gram
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Respiratory Exchange Ratio (RER)VCO2 / VO2; reflects “blend” of fat/CHO oxidized
0.70, pure fat
1.00, pure carbohydrate
assume negligible contribution from protein (i.e. non-protein RQ)
C6H12O6 + 6 O2 6 CO2 + 6 H2O (RER = 6 CO2 / 6 O2 = 1.00)
C16H32O2 + 23 O2 16 CO2 + 16 H2O (RER = 16 CO2 / 23 O2 = 0.70)
measured at lungs (i.e. whole body), but in theory, reflective of Respiratory quotient (RQ; at level of mitochondrion)
influenced by non-steady state conditions (VCO2)http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
RER is a relatively sensitive scale i.e. differences of 0.02 units translate to substantial differences in energy derived from each substrate
Example: exercise at ~ 75% VO2 max (3.0 L/min) for 60 min
If average RER = 0.80 (i.e. 2.4 / 3.0):
4.801 kcal/L O2 x 3.0 L/min x 60 min = 864 kcal
33.4 % kcal from CHO = 289 kcal
66.6 % kcal from fat = 575 kcal
If average RER = 0.82 (i.e. 2.46 / 3.0):
4.825 kcal/L O2 x 3.0 L/min x 60 min = 869 kcal
40.3 % kcal from CHO = 350 kcal
59.7 % kcal from fat = 519 kcalhttp://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Energy OUT
Total Daily Energy Expenditure (TDEE)
RMR
TEF
TA
Total Daily Energy Expenditure (TDEE)
RMRResting/basal Metabolic Rate (60-75%) “essential” (maintenance of ionic gradients, substrate cycles, etc.)
ion homeostasis, 40-60% (20-30% from Na/K ATPase alone)
protein turnover, 25%
mitochondrial uncoupling, 20-30%
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
main contributing tissues: skeletal muscle and liver (despite its small mass!)
Tissue Contribution (%) Mass (%)
Liver 26 3
Muscle 26 40
Brain 18 2
Heart 9 < 1
Kidneys 7 < 1
other 14
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Total Daily Energy Expenditure (TDEE)
TEF-- Thermic Effect of FoodAlso known as specific dynamic action (SDA) and heat increment of feeding (HIF)
obligatory (digesting, absorbing, assimilating)
facultative (stimulatory effect on metabolism, SNS)
mixed meal elevates RMR by 25-50%, but only lasts ~2-4 hours
splanchnic (gut, liver, pancreas) VO2 increases 50%
muscle (leg) VO2 increases 30%
thermic effect reduced in obese individualshttp://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
also, note that the metabolic consequences of individual macronutrients differ considerably
amino acids; 50% increase in splanchnic VO2
glucose; 8-13% increase in muscle VO2
fat; little change in VO2
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Total Daily Energy Expenditure (TDEE)
PA Physical Activity (15-30%)
http://www.uoguelph.ca/hb+ns/NUTR4210/BasicNotes.pdf
Energy Balance
Body weight
Food
RMR
TEF
PA
What controls energy intake?
The glucostatic theory
The liposatic theory
ob/ob mouse
Science 1996 December 6; 274: 1704-1707.
Fig. 1. Physical appearance and body weights of normal (OB/OB), ob/ob, and NPY/ ob/ob mice. (A) Representative body shapes of male mice at 15 weeks of age. Photo was cropped at mid-tail level. (B and C) Body weights of male and female mice at various ages. Values are the mean ± SEM; n > 10 for each group.
Science 1996 December 6; 274: 1704-1707.
Leptin
Body weight of NPY/ ob/ob females was significantly lower than that of ob/ob females at all ages after 6 weeks (P < 0.01). Body weight of NPY/ ob/ob males was significantly lower than that of ob/ob males at all ages after 10 weeks (P < 0.02).
Science 1996 December 6; 274: 1704-1707.
Fig. 2. Adiposity of normal, ob/ob, and NPY/ ob/ob mice. (A) Fat-selective magnetic resonance images (MRIs) of male mice at 14 weeks of age (12). Images are 3-mm thick, body length, horizontal sections. Adipose tissue appears white. Images are oriented such that the head of each mouse is at the top. The sides of the ob/ob image are straight because the mouse was pressed against the walls of the MR tube.
Science 1996 December 6; 274: 1704-1707.
(B) Average lipid:water ratios of 12- to 15-week-old mice obtained from MR spectra (12). Values are the mean ± SEM. Each group consisted of four males and three females. *P < 0.001 compared to ob/ob mice; unpaired t-test. Some ob/ob mice, but not double mutants, could not be analyzed by this technique because they were too large to fit into the 4.2-cm-diameter coil. Consequently, the adiposity of ob/ob mice was slightly underestimated. (C) Combined weights of inguinal, retroperitoneal, scapular, and reproductive pads, measured when mice were 16 weeks of age. Values are the mean ± SEM. The ob/ob group consisted of 19 males and 15 females; the double mutant group consisted of 12 males and 10 females. **P < 0.001 compared to ob/ob mice, unpaired t-test.
Science 1996 December 6; 274: 1704-1707.
Agouti Related Proteins
Agouti mouse
http://www.bioscience.org/news/scientis/leptin1.htm
The evidence so far…
A few years later ….
Glucostatic theory
Lipostatic theory
Ghrelin
DIABETES, VOL. 50, AUGUST 2001 Cummings et. al
http://endo.endojournals.org/cgi/reprint/142/10/4163.pdf
Candidate signaling molecules involved in energy homeostasis
Catabolic Anabolic
CRH* NPY* *MSH AGRP* CCK MCH Bombesin orexins A and B (=hypocretins 1 and 2) Somatostatin galanin Thyrotropin-releasing hormone
b-endorphin Calcitonin-gene– related peptide
dynorphin Neurotensin norepinephrine Glucagon-like peptide–1
growth hormone– releasing hormone
Serotonin * These molecules are particularly important in the regulation of adiposity.
The role of satiety signals in regulation of food intake
Integration of adiposity signals and satiety signals
Long term regulation of body weight
The evidence so far…
Glucostatic theory Lipostatic theory
A simplified model of the action of ghrelin and leptin on feeding-regulatory circuitry. Leptin acts as part of a feedback loop to maintain constant stores of fat5. Leptin is
released from adipocytes as a function of the amount of fat, and reduces food intake by acting on two hypothalamic pathways. It stimulates an anorexigenic pathway and inhibits anorexigenic pathway; both of them originate in the arcuate nucleus of the hypothalamus andproject to the paraventricular nucleus and the lateral hypothalamic area
Ghrelin is released from the stomach. The effect of ghrelin in the hypothalamus is opposite to that of leptin; in other words, ghrelin acts as an orexigenic molecule. In addition, ghrelin stimulates both energy gain and the secretion of growth hormone (GH) by acting directly on the anteriorpituitary. So, the action of ghrelin constitutes an integrated means to produce an anabolic state and growth. Fasting decreases leptin and increases ghrelin production, leading to the activation of the orexigenic pathway. This response might be important for adaptation to fasting. Although ghrelin is also produced by hypothalamic cells, it remains to be seen whether this source has a similar action to ghrelin produced by the stomach. GHRH, growth-hormone-releasing hormone.
Nature Reviews Neuroscience 2; 551-560 (2001);
What controls energy expenditure?
Uncoupling Proteins
Uncoupling proteins
UNCOUPLING PROTEINS
A 32 000 molecular weight uncoupling protein (now termed uncoupling protein-1, or UCP1)
located in the inner mitochondrial membrane of BAT. UCP1, which exists in active and
inactive forms, is unique to brown fat and as such differentiates the two forms of adipose
tissue (brown and white); it also appears to be restricted to mammals. A family of
mammalian uncoupling proteins has now been identified – UCP1, UCP2, UPC3, BMCP1 (and
perhaps UCP4) – with homologues in birds and plants. UCP2 has a wide tissuedistribution,
but is found particularly in white adipose tissue and cells of the immune system, while UCP3
is primarily expressed in skeletal muscle. Although these proteins were initially thought to
act as uncouplers in a manner analogous to UCP1, it is increasingly clear that this is not the
case. UCP2 and UCP3 may in practice be involved in lipid oxidation or play a role in
antioxidant defence. A role for UCP1 and for brown adipose tissue as a locus for adaptive
thermogenesis in relation to energy balance, as well as in thermoregulation, in rodents is
well established. However, the extent to which brown fat thermogenesis normally occurs in
adult humans remains problematic. Nevertheless,UCP1 is present in certain adipose tissue
depots throughout life and increased levels (indicating activation of brown fat) are evident in
patients with pheochromocytoma.Research Symposium – Human Energy Metabolism J Physiol (2003) 547.S Paul Trayhurn
A new view on…
www.deltagen.com/.../ adipose_tissue_white_40x.jpg
www.nature.com/tpj
The pharmacogenomics journal (2202) 2 :4-7 Ravussin, E.
www.nature.com/tpj
The pharmacogenomics journal (2202) 2 :4-7 Ravussin, E.
The seminal proposal by Steppan et al. suggested resistin to be a hormone that links obesity to diabetes. It was originally named for its resistance to insulin. Resistin serum levels were increased in obesity and resistin gene expression was induced during adipocyte differentiation (Fig. 1).
Conclusions
Although the first report proposed resistin serum levels to be increased in the obese
state, a number of later publications have demonstrated decreased resistin gene
expression in obesity. The way resistin was measured and the differences between
serum concentrations and mRNA and protein levels probably contribute to the
inconsistency observed in these studies. However, this does not necessarily rule out
the possibility that resistin could still play a role in metabolic disorders. Some recent
genetic studies have demonstrated an association between resistin and insulin
resistance and obesity.
www.eje.org
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2002) 147
There are four general classes of antiobesity drugs.
(i) Inhibitors of energy (food) intake (or appetite suppressants) reduce hunger perception, increase the feeling of fullness, and reduce food intake by acting on brain mechanisms. As a result, these drugs facilitate compliance with caloric restriction.
(ii) Inhibitors of fat absorption reduce energy intake through a peripheral, gastrointestinal mechanism of action and do not alter brain chemistry.
(iii) Enhancersof energy expenditure act through peripheral mechanisms to increase thermogenesis without requiring planned increases in physical activity.
(iv) Stimulators of fat mobilization act peripherally to reduce fat mass or decrease triglyceride synthesis or both without requiring planned increases in physical activity or decreases in food intake.
Magainin Pharmaceuticals MSI-1436, a novel drug.
MSI-1436 appears to act differently than any other appetite suppressant. The compound may interact with calmodulin, a calcium sensing protein, to alter calcium signaling within certain cells of the brain. Squalamine, now in Phase 2 cancer trials (July 2000), is the first aminosterol discovered in the dogfish shark and works by sequestering calmodulin within the cell.http://www.obesity-news.com/omr08-00.htm#ucp3 MSI-1436 may interact with calmodulin, a
calcium sensing protein, to alter calcium signalling within certain cells of the brain.
http://www.obesity-news.com/omr08-00.htm#ucp3
New lipase inhibitor completes phase 1 trial.Alizyme plc announced on July 7 2000 that it successfully completed a Phase 1a clinical trial of its obesity drug ATL-962. ATL-962 is a lipase inhibitor that works similarly to the drug Xenical. ATL-962 is the only other lipase inhibitor being developed besides Hoffmann-LaRoche's Xenical. In pre-clinical studies the drug had similar efficacy to the Roche drug, and no toxicity was observed.