Energy Balance Applied Human Metabolism VII Weight Regulation The balance of energy taken in or leaving the body determines body mass Energy In = Energy Out Weight Maintenance Energy In < Energy Out Weight Loss Energy In > Energy Out Weight Gain Energy Out Factors that effect BMR/RMR We can loose weight in theory by increasing the amount of energy we expend Components of daily energy expenditure (energy out) MR = MetaboilcRate BMR=Basal MR DIT = Dietary-induced thermogenesis Let s briefly consider these Measured Metabolic Rate Physical Activity DIT Arousal RMR Basal MR 1
Effect of Endurance Training on Total Energy Expenditure in the Elderly Pre training TEE = 2405 kcal/day During Training TEE = 2474 kcal/day We conclude that in healthy elderly persons, endurance training enhances cardiovascular fitness, but does not increase TEE [Total Energy Expenditure] because of a compensatory decline in physical activity during the remainder of the day. TEM =thermiceffect of meal EEPA = Energy expenditure due to Physical activity Goran& Poehlman. (1992) Am. J. Physiol. 263: E950 Exercise is pretty good at helping you maintain weight But to lose it we really need to control energy in Types of Thermogenesis Thermogenesisis the generation of heat by the body There are several classes of thermogenesis Increasing thermogenesis can aid weight loss We need to control appetite 2
Thermogenesis induced by food Two types Thermogenesisdue to increased metabolism of the gastro-intestinal tract due to digestion Thermogenesisdue to activation of the sympathetic nervous system Occurs after eating usually starting after around 10 minutes Lasts only around 4 hours BMR raised to a level between 5% and 100%, but more usually 10% for a mixed meal Different thermogenicrates for macronutrients Ethanol > protein > carbohydrate > fat Available from: http://www.nutritionandmetabolism.com/content/pdf/1743-7075-1-5.pdf A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Available from: http://www.nature.com/ijo/journal/v23/n11/pdf/0801108a.pdf Easy to understand thermic effect by digestive metabolism but why involve the sympathetic nervous system? Animal studies indicate that DIT evolved mainly to deal with nutrient-deficient or unbalanced diets, and re-analysis of twelve overfeeding studies carried out between 1967 and 1999 suggests the same may be so for humans, particularly when dietary protein concentration is varied. 3
17/03/2016 DIT and Evolution Why should a system which has a role in preventing weight gain by wasting food, have evolved? Stock suggested DIT may not be used when diets are well balanced in terms of essential nutrients, but may be very important when diets are low in these DIT may have evolved to allow individuals to over-eat relatively large quantities of poor quality food to obtain essential nutrients without deposition of excess, nonessential energy as fat (excessive body mass would impede locomotion and hunting) DIT may have evolved as a means of regulating metabolic supply of protein, minerals and vitamins Dietary Induced Thermogenesis Sympathetic Nervous System (SNS) Landsberg et al. (1984) showed that the SNS activity (in a variety of tissues) is increased during overfeeding and decreased during starvation (energy conservation) Norepinephrine (a neurotransmitter) Kurpad et al. (1994) showed that in adult humans infusion of norepinephrine increases RMR Controls pathways increasing consumption of ATP Controls pathway leading to increased rate of oxidation in mitochondria (with poor coupling of ATP synthesis and leading to increased heat production) in brown fat The game changing paper however was Available from Academic Search Complete Brown (& Beige) fat The SNS is now known to activate brown and beige fat by secreting norepinephrine These two types of fat (as opposed to white fat) generate heat we created mice that lack the three known ßARs [ß-adrenergic receptor] (ß-less mice), ß-less mice on a Chow diet had a reduced metabolic rate and were slightly obese. On a high-fat diet, ß-less mice, in contrast to wild-type mice, developed massive obesity that was due entirely to a failure of diet-induced thermogenesis. These findings establish that ßARs are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity. This is done by uncoupling the electron transport system in the mitochondria The proton gradient dissipates but no ATP is made 4
Brown Adipose Tissue Heat Generation Summary Brown Adipose Tissue (BAT) inactivation It has been suggested that inactivation of BAT can lead to obesity Excess calories are not oxidised Available from: http://ajcn.nutrition.org/content/40/3/542.full.pdf Am J Clin Nutr September 1984 vol. 40 no. 3 542-552 The thermogenicresponse to the three meals (expressed in percentage of the total energy ingested) was found to be blunted in obese women. 5
Available from: http://ajcn.nutrition.org/content/40/3/542.full.pdf Am J Clin Nutr September 1984 vol. 40 no. 3 542-552 In addition, the relative increase in diurnal urinary norepinephrineexcretion was lower in obese than in the control subjects. It is concluded that a low overall thermogenicresponse to feeding may be a contributing factor for energy storage in some obese subjects; a blunted response of the sympathetic nervous system could explain this low thermogenic response. So how do we induce Brown and Beige fat? Cold β-agonists Induced by protein in the diet Induced by a ketogenic diet Activators of Brown Fat 6
Energy In Hunger is controlled by neurons in the arcuate nucleus situated in the hypothalamus But it is complex Partial List of Systems Involved in Hypothalamic Control of Food Intake Leptin Insulin Amylin NPY CRH UCN UCN II Galanin Neurotensin CART Oxytocin α-msh Corticosterone Serotonin Dopamine MCH Orexins Histamine Ghrelin GLP-1 GLP-2 AgRP Beacon Cannabinoids TNFα Beta-Endorphin Dynorphin BDNF PYY IL-6 IL-1 IL-1RA Norepinephrine Amino Acids PRL-RL GAL-LP Hunger vs. Appetite Hunger: physical need for energy, accompanied with unpleasant symptoms such as weakness, stomach pains, irritability Appetite: desire to eat is driven by mental stimuli It is one of the major reasons we over eat We eat to be social for instance You eat more when you eat with your mother When you eat chicken and the bones are cleared immediately, you will eat more than if you allow the bones to pile up Appetite is thus dictated by your lifestyle Hunger Control NPY/AgRPwhen synthesised produces ravenous eating POMC/CART/αMSH when synthesised inhibit appetite Synthesis is induced/repressed by several hormones 7
Orexigenic& Anorexigenic agents Anorexic agents are appetite suppressors POMC & CART Orexigenic agents are appetite stimulants NPY & AGRP Leptin Expressed only by fat cells Reflects quantity of body fat Fat Leptin Appetite NPY suppressed & POMC stimulated Leptin levels in the blood Circulating levels of leptinare directly related to fat mass i.e. it is secreted by adipose tissue [Leptin] Stop eating reserves are high Start eating reserves are low Fat Mass In this way leptinindicates long-term energy balance Leptin& Insulin In the short-term (meal to meal) insulin has an effect on leptin If you inject insulin you find leptinlevels increase. Increased insulin thus can suppress appetite via leptin i.e. Respond to shortterm energy balance 8
Amylin,or Islet AmyloidPolypeptide(IAPP), is a 37-residue peptide hormone. [1] It is cosecretedwith insulinfrom the pancreatic β-cellsin the ratio of approximately 100:1. Amylinplays a role in glycemicregulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels. So how does a low CHO diet suppress appetite? It is because it is high protein and helps control Ghrelin Ghrelin Ghrelinis secreted by gastric epithelial cells A gurgling stomach implies ghrelin production Activation of gastric stretch receptors inhibit ghrelinproduction. Increased ghrelin stimulates expression of NPY Inhibits vagus nerve Ghrelin: Meals Adapted from Cummings et al. (2001) Diabetes 50:1714 9
Available from here PYY 3-36 A peptide secreted by L-cells in the GI mucosa in proportion to calorific intake (mainly colon and ileum) The [High Protein] breakfast decreased postprandial ghrelinconcentrations more strongly over time than did the [High Carbohydrate] breakfast. Decreasesfood intake by inhibiting NPY & AgRP synthesis The GI tract is very good at estimating the calorific value of a meal Available from here The relationship of AMPK & Hunger In normal-weight and obese human subjects, highprotein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. 10
Gut Peptides That Regulate Appetite Murphy KG, Bloom SR. Nature. 2006;444:854-859. Murphy KG, Bloom SR. Nature. 2006;444:854-859. Gut Peptides That RegulateAppetite Second order neurons and nerves Neuroregulation of Energy Balance POMC/CART & NPY/AgRPare called first order neurons They are close to a weak/permeable area of the blood brain barrier Thus they can monitor blood-borne hormones like leptin However the effects of hunger and satiation are promoted by many other second order neurones such as: Paraventricular nucleus Ventral medial nucleus Nerves of the parasympathetic and sympathetic nerves are also involved Leptin Insulin Adiposity Signals PYY GLP-1 PP OXM CCK Satiety Peptides Ghrelin Hunger Signals Vagus nerve Food Status signals 11
SPA (and resulting NEAT) regulatory brain areas and associated neuropeptides/transmitters [updated from fig. 1 in Kotz(Kotz, 2008)]. The link to thyroid function 2011 by The Company of Biologists Ltd Theodore Garland, Jr et al. J Exp Biol 2011;214:206-229 ARC = Arcuate nucleus PVN = Paraventricular nucleus http://www.hindawi.com/journals/jtr/2011/306510/ Higher Brain Functions The hunger and satiety signals we have considered are part of a much bigger system that integrates and balances many aspects The second order neurones we have briefly covered also interact with higher order brain functions that may be considered to code for subjective views on feasting and fasting For instance, if you think about you favourite food you are more likely to feel hungry If you imagine eating it several times however, you will desire it less with each imaginary round of eating Genetics also wade in making responses vary Available from: http://onlinelibrary.wiley.com/doi/10.1038/oby.2004.110/epdf Obesity Research Volume 12, Issue 6, pages 904 912, June 2004 Studies suggest that the inherited ability to taste bitter thiourea compounds such as phenyl-thiocarbamideand 6-n-propylthiouracil (PROP) It has been hypothesized that individuals who are more sensitive to PROP avoid bitter and strong tasting foods. Some, but not all, studies have reported that PROP tasters show lower acceptance of cruciferous and other bitter vegetables and fruits and higher acceptance of fatty foods such as high-fat salad dressings and spreads, whole milk, and cheeses. Several of these observations have come from studies in children. 12
Available from: http://onlinelibrary.wiley.com/doi/10.1038/oby.2004.110/epdf Obesity Research Volume 12, Issue 6, pages 904 912, June 2004 Questions This study is the first, to our knowledge, to report weight differences in children as a function of their PROP status. Genetic taste factors seem to play a role in the development of dietary patterns and weight differences in young children, but the nature of these relationships may vary with gender. 13