1st MBBS Energy Metabolism Live Dr CK Student Version 2023-24.pptx

ISCM UM1010 2023-24 Energy Metabolism Dr Chiranjeevi [email protected] 1st December 2023 Venue: HALT 9:00 to 10:00 AM  Learning Objectives  Examining the concept of energy balance and factors that affect it....

ISCM UM1010 2023-24 Energy Metabolism Dr Chiranjeevi [email protected] 1st December 2023 Venue: HALT 9:00 to 10:00 AM  Learning Objectives  Examining the concept of energy balance and factors that affect it.  Looking at changes in energy requirement throughout life.  Identifying health conditions related to negative energy balance.  Describing health conditions related to overweight and obesity (positive energy balance). 01/12/2023 Energy Metabolism - Dr CK - 2023-24 2  Discussing theories of control of eating. Energy balance and laws of Thermodynamics First law of Thermodynamics Energy intake= Energy Expenditure+ Change in energy stores Chemical energy obtained from food can be used to perform a variety of work: Synthesis of new macromolecules: CHEMICAL WORK Muscular Contraction: MECHANICAL WORK Maintenance of isotonic gradients across membranes : ELECTRICAL WORK Energy expenditure + Work done + Heat Generated 01/12/2023 Energy Metabolism - Dr CK - 2023-24 3 Energy Balance Food Intake in excess of energy expenditure = Positive Energy balance Food intake less than energy expenditure = Negative energy balance A severe negative energy balance can lead to a decline in metabolism, decreases in bone mass, reductions in thyroid hormones, The catabolism of nutrients provides energy reductions in testosterone levels, an inability to the body in a controlled way. to concentrate, and a reduction in physical Dietary intake must be approximately equal performance. to energy expenditure for homeostasis. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 4 Metabolic substrates – carbohydrates, lipids and proteins SI units are kJ, although in UK kCal is more commonly used 1g of lipids contain 9kCal (37kJ) 1g of protein contains 4kCal (17kJ) 1g of carbohydrate contains 4kCal (17kJ) The energy stored within the chemical bonds of the substrates is released during catabolic reactions within all cells The SI unit of energy is the joule (J), and 1 kJ=0.239 kcal. The conversion factor of 4.2 kJ, equivalent to 1.00 kcal, is used in clinical nutrition 01/12/2023 Energy Metabolism - Dr CK - 2023-24 5 Catabolic and Anabolic reactions Catabolism- oxidation of carbohydrates, proteins and fats to produce carbon dioxide and Water and ENERGY Anabolism- Energy can be stored in the form of energy rich phosphate compounds and in the form of proteins, fats and complex carbohydrates 01/12/2023 Energy Metabolism - Dr CK - 2023-24 6 Energy Balance - Energy Requirement Varies with age How much energy is required for an Varies with sex individual for normal Varies with activity 01/12/2023 day-to-day Energy Metabolism activities? - Dr CK - 2023-24 level 7 Factors determining energy intake It is though that we have centres in the hypothalamus that control the desire to eat, which are influenced by a variety of factors. Orexigenic or Anorexigenic The amount eaten is determined by satiation (feeling of fullness) and satiety (reduced interest inS.J., Guyenet, food). & Schwartz, M.W. (2012). Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesity. The Journal of clinical endocrinology and metabolism, 97 3, 745-55. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 8 Factors that may contribute to control of energy intake Cholecystokinin released Stretch receptors in the Ghrelin (a from mucosa in small stomach initiate neural peptide) is intestine in the presence of signals to the satiation secreted from the protein and fat; triggers centre gastric mucosa ; reduction in food intake via known to increase vagal afferent nerves feeding behaviour but blood levels Leptin (hormone) secreted not always Reward signals – e.g. by adipocytes when fat is correlated with palatability (Tastiness). Cause stored; acts as a negative initiation of release of dopamine in the feedback regulator of feeding so role brain which result in positive adiposity via leptin receptors uncertain reward sensation; reduces in the hypothalamus amount of food eaten 01/12/2023 Energy Metabolism - Dr CK - 2023-24 9 Feedback mechanisms for controlling food intake Stretch receptors in the stomach activate sensory afferent pathways in the vagus nerve and inhibit food intake. Peptide YY (PYY), cholecystokinin (CCK), and insulin are gastrointestinal hormones that are released by the ingestion of food and suppress further feeding. Leptin is a hormone produced in increasing amounts by fat cells as they increase in size. It Dietaryfood inhibits Balances; Regulation of Feeding; Obesity and Starvation; intake. Vitamins and Minerals Hall, John E., PhD, Pocket Companion to Guyton and Hall Textbook of Ghrelin is released by the stomach, especially Medical Physiology, Chapter 72, 515-525 01/12/2023 Energy Metabolism - Dr CK - 2023-24 10  Effects of Leptin and Ghrelin Leptin and Ghrelin act reciprocally on food intake Both activate signaling in the Hypothalamus Leptin is produced by adipose tissue and signals the status of fat stores As adipocytes increase in size, they release more Leptin which tends to decrease food intake Ghrelin- is fast acting – produced mainly. by the stomach in response to changes in nutritional status Circulating levels increase preprandially and then decrease after a meal. Ghrelin to be involved in meal initiation unlike longer acting Leptin. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 11 Overeating and consequent obesity Leptin (hormone) secreted by Overeating and consequent adipocytes when fat is stored; obesity may be a result of leptin acts as a negative feedback resistance (so the feedback regulator of adiposity via leptin signals are not received) receptors in the hypothalamus Both may be either a cause or a result of obesity Reward signals – e.g. Reduced sensitivity of D2 palatability, association, energy receptors (for dopamine) may density. Cause release of also contribute to overeating, dopamine in the brain which causing individuals to eat result in positive reward more/more energy dense food sensation; reduces amount of 01/12/2023 in order to achieve the same Energy Metabolism - Dr CK - 2023-24 12 Homeostatic Regulation of food intake Blundell et.al 2015 Appetite control and energy balance : impact of exercise 01/12/2023 Energy Metabolism - Dr CK - 2023-24 13 Energy Balance – Energy Expenditure 01/12/2023 Energy Metabolism - Dr CK - 2023-24 14 Energy Balance – Energy Expenditure Total Energy Expenditure (TEE) It is the number of calories burned by the human body in one day is composed of 20- three primary factors: 30% 10% Resting Energy Expenditure or basal metabolic rate Thermic effect of food 60- 70% Activity - Activities of daily living (ADL) - physical activity (PA) 01/12/2023 Energy Metabolism - Dr CK - 2023-24 15 Definition of BMR, Energy Expenditure & Metabolic Rate Basal metabolic rate is the energy released when the subject is at complete mental and physical rest i.e. in a room with comfortable temperature and humidity, awake and sitting in a reclining position, 10- 12 hours after the last meal. It is essentially the minimum energy required to maintain the heart rate, respiration, kidney function etc. Total energy expenditure depends on the BMR, the energy required for physical activity, and the energy cost of synthesizing reserves in the fed state 01/12/2023 Energy Metabolism - Dr CK - 2023-24 16  Factors affecting BMR Basal/ resting– BMR Typically accounts for 60-75 % of daily expenditure Genetics Circulating levels of thyroid Age - BMR reduces with age hormones Gender - Men have a higher BMR than women Circulating epinephrine and Height, weight, and surface area norepinephrine levels Muscular exertion during or just before Growth measurement Reproduction Recent ingestion of food Pregnancy & Lactation 01/12/2023 Energy Metabolism - Dr CK - 2023-24 17 Basal metabolic rate – Determinants Most important determinant of BMR is ‘Body Size’ For example: Body size is determined by body composition (BF and FFM). Fat mass/body fat & and Fat free mass/lean body mass are influenced by age, gender, height and weight. Which individual do you think to have a higher basal metabolic rate, a normal weight adult or obese adult? The BMR of overweight and 01/12/2023 obese Energy people Metabolism is higher than - Dr CK - 2023-24 18 Resting Energy Expenditure vs BMR Basal metabolic rate (BMR) vs resting metabolic rate (RMR) While BMR is the minimum number of calories required for basic functions at rest, RMR — also called resting energy expenditure (REE) — is https://doi.org/10.1002/ oby.23090 the number of calories 01/12/2023 Energy Metabolism - Dr CK - 2023-24 19 Resting Energy Expenditure Resting Energy Expenditure - what uses all this energy? Organs with high energy needs total only 5% of body weight, yet use 58% of REE: - liver = 21% of total REE; brain 20%; heart 9%; kidneys 8% Muscle EE is only 3% of heart’s EE/g at rest, but in total comprises 22% of RMR at rest Adipose tissue is even lower EE/g, and is always at rest: 4% of RMR in lean, up to https://doi.org/10.1002/ 01/12/2023 10% in obese people Energy Metabolism - Dr CK - 2023-24 oby.23090 20  Estimating BMR and REE There are several equations that can be used to estimate energy expenditure ; the original one was the HARRIS – BENEDICT equation The one below is the current Institute Of Medicine Equation For Estimated Energy 01/12/2023 Energy Metabolism - Dr CK - 2023-24 21 Requirement (EER)  TEF is the energy cost of digestion, absorption, processing and storage of nutrients. Thermic effect of feeding TEF (or Comprises about 10% of TEE in sedentary feeding/diet induced individuals thermogenesis, FIT/DIT) There are no significant differences in between ages or gender Lower TEF is often seen in obese individuals 01/12/2023 Energy Metabolism - Dr CK - 2023-24 22 Diet Induced Thermogenesis There is a considerable increase in metabolic rate after a meal -diet- induced thermogenesis The major part is the A mixed diet consumed energy cost of at energy balance can synthesizing reserves of Protein can play result in 5-15% of daily glycogen, an important role energy expenditure triacylglycerol, and in body weight protein. regulation through satiety related to diet A small part of this is the induced Hierarchy in macronutrient energy cost of secreting thermogenesis oxidation in the digestive enzymes and. postprandial state is of active transport of alcohol, protein, CHO, and the products of fat. digestion 01/12/2023 Energy Metabolism - Dr CK - 2023-24 23 Physical activity in Energy Expenditure The rate of energy expenditure ranges from behaviours with very low energy expenditure, such as sleep, to vigorous activities with high energy expenditure such as sprinting Physical activity encompasses all movement of at least light intensity, and extends to movement of moderate and vigorous intensity British Heart Foundation National Centre for Physical Activity and Health. Evidence Briefing: Sedentary Behaviour2012. Available from: http://www.bhfactive.org.uk. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 24 Energy Requirements Increase With Activity The most useful way of expressing the energy cost of physical activities is as a multiple of BMR. This is known as the physical activity ratio (PAR) or metabolic equivalent of the task (MET). Sedentary activities use only about 1.1 to 1.2 × BMR. By contrast, vigorous exertion, such as climbing stairs, cross-country walking uphill, etc, may use 6 to 8 × BMR. The overall physical activity level (PAL) is the sum of the PAR of different activities, 01/12/2023 multiplied Energy Metabolism - Dr by CK - the time 2023-24 25  Energy Requirements Increase With Activity Sedentary or light activity: TEE = 1.53 × 5.40 = 8.26 MJ (1 975 kcal), or 150 kJ (36 kcal)/kg/d. Active or moderately active: TEE = 1.76 × 5.60 = 9.86 MJ (2 355 kcal), or 173 kJ (41 kcal)/kg/d. Vigorous or vigorously active: TEE = 2.25 × Energy Metabolism - Dr CK - 2023-24 01/12/2023 26 7.30 = 16.42 MJ (3 925 kcal), or 235 kJ (56 Eat less or exercise more? Making progress on the global crisis of obesity and weight management BMJ 2018; 361 doi: Although exercise has a small weight loss https://doi.org/10.1136/bmj.k2538 (Published 13 benefit. June 2018) When combined with an energy restricted food plan, neither aerobic nor resistance exercise in typical amounts are effective as a sole strategy. Reducing energy intake has the central role in weight loss and prevention of regain will help prevent discouragement. Physical activity has a modestly greater role in maintaining weight loss and undoubted value for long term health and preserving muscle mass. ‘Weight loss maintenance is a greater challenge than weight loss for many people because it requires adapting to permanently eating less energy despite living with in the same physical, social, cultural, and educational 01/12/2023 Energy Metabolism - Dr CK - 2023-24 27 environments in which they developed obesity’  Activity kCal per Total EE in Exercise and EE min 10 min (kCal) Depends on type of exercise e.g. for a person Step 7.4 74 weighing 70kg performing activity for 10 mins aerobics Cycling 6.4 64 Calories used in 15kph Physical activity 30 minutes Ironing 69 Walking 4.1 41 5kph Cleaning and dusting 75 1lb (pound) of Walking 99 Vacuum cleaning 105 body fat is Golf 129 equivalent to Tennis (doubles) 150 Brisk walking 150 3500 kCal Mowing the lawn (using a (14644kJ) 165 power-mower) Cycling 180 Aerobics 195 1kg body fat is Swimming (slow crawl) 195 Tennis (singles) 240 equivalent to Running (10 minutes/mile) 300 7700kCal Running (8.5 minutes/mile) 345 Running (7.5 minutes/mile) 405 (32217kJ) 01/12/2023 Energy Metabolism - Dr CK - 2023-24 28  Diet ‘There's no single rule that applies to everyone, but to lose weight at a safe and sustainable rate of 0.5 to 1kg a week, most people are advised to reduce their energy intake by 600 calories a day. For most men, this will mean consuming no more than 1,900 calories a day, and for mostdietary Reducing women, no more than 1,400 calories a day.’ carbohydrate ortimes Fats contain two to three fat?as many calories per gram as carbohydrate and are more readily stored as body fat, without raising metabolic rate. Carbohydrates act as a more potent stimulus for insulin and possibly promote fat deposition. https://doi.org/10.1152/ ajpregu.00755.2010 01/12/2023 Energy Metabolism - Dr CK - 2023-24 Evidence comparing low carbohydrate and low- 29 Summary of Energy Metabolism Energy is needed by the body to stay alive, grow, keep warm and move around. Energy is provided by food and drink. It comes from the fat, carbohydrate, protein and alcohol the diet contains. Energy requirements vary from one individual to the next, depending on factors such as age, sex, body composition and physical activity level. Energy expenditure is the sum of the basal metabolic rate (the amount of energy expended while at complete rest), the thermic effect of food (TEF, the energy required to digest and absorb food) and the energy expended in physical activity. To maintain body weight, it is necessary to balance the energy derived 01/12/2023 Energy Metabolism - Dr CK - 2023-24 30 from food with that expended in physical activity. To lose weight, Summary of Energy Metabolism Making progress on the global crisis of obesity and weight management Adaptive changes BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k2538 (Published 13 June 2018) At any weight, a person whose body weight and physical activity remain stable must consume the same number of calories as are expended. As weight (body mass) increases, basal metabolism and the cost of carrying the extra weight in activities both rise gradually, roughly in proportion to the weight gain. So continued weight gain will occur only if the calories consumed continue to rise. During active weight loss, basal metabolic rate falls and physical activity becomes more efficient, so fewer calories are expended in proportion to weight loss. Additionally, severe negative energy balance (i.e. undereating) produces exaggerated adaptive changes. These changes protected people against food shortages during evolution, such that consuming a fixed calorie deficit below the baseline energy expenditure will lead to weight loss but with a plateau. For continued weight loss, to treat obesity, energy intake must fall further to remain at a level 01/12/2023 Energybelow the- Drreduced Metabolism energy expenditure. CK - 2023-24 31 Overview of Obesity Overweight and obesity are defined as abnormal or excessive fat accumulation that presents an adverse health effects. [WHO] Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults *Obesity is a long-term (chronic) health condition that progresses over time. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 32 Is obesity dangerous? Excess adiposity (obesity) and excess body weight are associated with increased incidence of several diseases of humans. Type 2 diabetes, Dyslipidaemias, Hypertension, Cardiovascular diseases & Cancer. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 33 Measures of Obesity The most widely used measure of obesity is the Body Mass Index (BMI), defined as weight in kg divided by the square of height in meter (kg/m2). A person is classified as obese if their BMI is 30 or higher. A BMI of 40 or more is often known as ‘morbid obesity’. This measure is not always definitive, and sometimes other measures are used. waist circumference and hip circumference waist-hip ratio (defined as the waist circumference divided by the hip circumference which provides an indication of the distribution of fat on the body). 01/12/2023 Energy Metabolism - Dr CK - 2023-24 34 BMI – Pros and Cons Advantages Disadvantages  Easy to measure and to  Not reliable in children monitor  Simple and easy to  Not suitable for those with understand high lean body mass (i.e. high proportion of muscle)  Good indication of body  Does not represent fatness in the majority of percentage body fat people  Widely used in scientific  Does not give any indication journal articles, by health of central adiposity (increased reporting bodies and medical health risk) professionals 01/12/2023 Energy Metabolism - Dr CK - 2023-24 35 BMI & Waist circumference The National Institute for Health and Clinical Excellence (NICE) recommends the use of BMI in conjunction with waist circumference as the method of measuring overweight and obesity and determining health risks. BMI neither distinguish between body fat and mass due to muscular physique, nor the distribution of fat. To measure abdominal obesity, waist circumference is measured, and categorized into desirable, high and very high, by sex-specific thresholds (cm): Men: Desirable = Less than 94, High = 94-102, Very high = More than 102 01/12/2023 Energy Metabolism - Dr CK - 2023-24 36 Waist to Hip Ratio Advantages Disadvantages Ratio of smallest  Quick, requires no  Needs to be done waist expensive equipment carefully to get an measureme accurate measurement nt to widest  Can be done easily in a  Unsuitable for pregnant hip surgery or clinic women measureme World nt. Health  Indicator of amount of  Inaccurate after a large organisation visceral fat, which is meal defines related to disease obesity as conditions WHR > 0.85  Does not measure in women and WHR > percentage fat 0.90 in men. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 37  Obesity – Chronic low-grade inflammation Obesity usually develops as a result of chronic imbalance between intake and expenditure. This is due to a positive energy balance - an excess of energy consumed versus energy Weight loss can reduce used in relation to basal metabolism and inflammatory mediators physical activity. The concept that obesity induces low-grade chronic inflammation in classical metabolic tissues has revolutionized the idea that obesity is strictly a metabolic disorder 01/12/2023 Energy Metabolism - Dr CK - 2023-24 38 Adipose Tissue Adipose tissue provides insulation and tissue support and is the body's major energy reserve, storing triglycerides and glycerol. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 39 Comparison between lean and obese adipose tissue – Obesity & Inflammation Zhao et al. Cellular Immunology (2018) 332, 1-6 Abbreviations: IL, interleukin; NO, nitric oxide; TNFα, tumor necrosis factor α. Cornide-Petronio ME et al. New Insights into the Liver-Visceral Adipose Axis During Hepatic Resection and Liver Transplantation. Cells. 2019 Sep 18;8(9):1100. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 40  Comparison between lean and obese adipose tissue – Summary Lean adipose tissue is Obese Adipose predominantly populated tissue(AT) is infiltrated by with regulatory cells, pro-inflammatory such as eosinophils and macrophages and T cells type 2 innate leading to the lymphocytes. accumulation of interleukin-1β (IL-1β), tumor necrosis factor α, IL- These cells maintain 17 and IL-6. tissue homeostasis through the excretion of Responsible for low-grade type 2 cytokines, such as inflammation, with the IL‐4, IL‐5, and IL‐13, infiltration of several which keep adipose classes of pro- tissue macrophages inflammatory immune cells (ATMs) in an anti‐ including monocytes, inflammatory, M2‐like macrophages, natural killer state cells, and lymphocytes. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 41  Functions of key adipokines secreted by adipocytes Energy Metabolism - Dr CK - 2023-24 01/12/2023 42  Obesity and Type 2 Diabetes  Obesity is thought to account for about 80- 85 % of the risk of developing Type 2 diabetes  Obese people are up to 80 to 85 times more likely to develop type 2 diabetes than those with a BMI of less than 22.  Type 2 diabetes is characterized by insulin resistance, impaired insulin secretion, glucose Insulin resistance: intolerance and hyperglycemia. Excess weight can produce insulin resistance, cells reduce  T2D is widely viewed as a chronic low grade sensitivity, do not respond, to inflammatory disease caused by long term insulin and glucose cannot immune system imbalance, metabolic enter them. syndrome and abdominal obesity. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 43   Obesity and Coronary Artery Disease  Increased blood lipid levels increase the risk of formation of fatty plaques in blood vessels  Hypertension also increases this risk as it causes damage to arterial endothelium, triggering an inflammatory response  Small blood vessels such as those supplying heart muscle are particularly at risk  As the lumen of coronary blood vessels decreases, the blood flow to sections of the cardiac muscle is progressively reduced  Early symptoms are those 01/12/2023 of angina; later can result in Energy Metabolism - Dr CK - 2023-24 44  Obesity and Hypertension and Heart Failure  Blood pressure is often increased in overweight individuals due to increased length of blood vessels and therefore increased total peripheral resistance.  Increased blood pressure means that the heart needs to work harder, leading to ventricular hypertrophy.  Ventricular hypertrophy causes stiffening of the ventricular walls and inefficient emptying, leading to heart failure. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 45  Gall stones in Obesity  Obesity appears to be associated with the development of gallstones.  Approximately 20 mg of additional cholesterol is synthesized for each kg of extra body fat, resulting in higher blood cholesterol levels in obese individuals  High cholesterol concentrations relative to bile acids and phospholipids in bile increase the likelihood of precipitation of cholesterol gallstones in the gallbladder.  Normally, a balance of bile salts, lecithin, and cholesterol keep gallstones from forming. However, if there are abnormally high levels of bile salts or, cholesterol, then stones can form 01/12/2023 Energy Metabolism - Dr CK - 2023-24 46  Ischemic stroke in Obesity  Ischaemic strokes occur when an artery to the brain is blocked.  Risk of Ischaemic stroke is increased in overweight and obesity. With increasing BMI, the risk of Ischaemic stroke increases progressively and is doubled in those with a BMI greater than 30 kg/m2 when compared to those having a BMI of less 01/12/2023 than 25 kg/m2 Energy Metabolism - Dr CK - 2023-24 47  Attempting weight loss to reverse the consequences of obesity  Losing weight also involves many other factors, such as motivation, available time, and cost of and access to appropriate weight-reduction programs.  Low-calorie diets contain approximately 1200–1300 kcal/day, and very-low-calorie diets contain around 800 kcal/day.  Limit energy intake from total fats and sugars;  Increase consumption of fruit and vegetables, as well as legumes, whole grains and nuts;  Engage in regular physical activity (60 min a day for children and 150 min spread through the week for adults).  Generally, a combination of diet and exercise plus behaviour interventions such as goal- setting and relapse avoidance is more effective in inducing weight loss than diet alone. 01/12/2023 Energy Metabolism - Dr CK - 2023-24 48  However, there are limited evidence-based interventions that can induce a weight loss Thanks ! 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