Homeostatic and Non-homeostatic (hedonic) control of weight regulation: Which wins? Amy Rothberg, MD, PhD August, 2016 International Congress of Endocrinology
Propensity to Obesity • Determined by genetics, epigenetics, and multiple environmental influences
Energy Balance - Homeostasis • Obesity is simply an energy balance where calories consumed are greater than calories expended Flegal et al. 2010
Propensity to Obesity • Determined by genetics, epigenetics, and multiple environmental influences
Why Do We Eat? There are two apparently conflicting points of view: Experimental evidence in animals and humans In contrast, population suggests that body evidence says that weight is tightly average body weight is regulated – the concept gradually increasing. of energy homeostasis. This reflects a fundamental tension between homeostatic and non-homeostatic controllers of food intake.
Regulation of appetite and energy balance The brain monitors the internal milieu through a • number of hormonal- and neural nutrient-sensing mechanisms. It is under constant influence of both environment • and lifestyle through the senses • through the cognitive and emotional brain. •
Hormones Transmitters Hypothalamus Nutrients NPY/AGRP & POMC/CART Signaling Cortico-limbic Autonomic & structures & endocrine Pathways hypothalamus systems Orosensory systems (brainstem) Assimilate, store, Seek & procure Eat –OR- Do NOT Eat mobilize, expend Adapted from: Huiyuan Zheng, and Hans-Rudi Berthoud Physiology 2008;23:75-83
Regulation of Eating Why we eat, what we eat and the amount we eat is governed by: Taste perception • Meal size (portion) • Caloric density • Environmental setting • Timing of meals • Composition • Under most circumstances, meal initiation is not controlled by metabolic or hormonal signals.
Environmental Factors • The food industry uses chemistry, engineering, psychology and mathematics to produce formulations that optimize consumer enjoyment 16
Environmental Factors Consumers base food choices on: HEALTH TASTE PRICE CONVENIENCE
Environmental Factors Others: SUPERSIZED HABIT/ PATTERN MACRONUTRIENT PORTIONS “ADDICTION”
ULTRA- PROCESSING- CHEAP FOOD!
Homeostatic Signals Our sense of hunger and fullness are determined by complex interactions between a number of peptides (proteins) and hormones from our: • digestive system (ghrelin, CCK, PYY) • adipose tissue (leptin) • pancreas (insulin) These relay signals from our gut to our brain. Mountjoy, Kyiv 2003
Important Hormones/Neurotransmittors: CCK PYY Insulin Leptin Ghrelin GLP-1 Apolipo Gluca- amylin GRP -protein gon A-IV Bombe- Oxynto- Neuro- sin modulin medin B (family)
Important Hormones/Neurotransmittors: a description Ghrelin (Q9UBU3) (ghre=growth) Polypeptide hormone produced by cells lining the fundus of the stomach and by Ε cells of the pancreas. It is also produced in the arcuate nucleus where it stimulates secretion of growth hormone by the anterior pituitary gland in the central nervous system. It increases smell sensitivity and makes food taste better. It has an orexigenic effect (stimulates food intake). • GH • hunger
Important Hormones/Neurotransmittors: a description Ghrelin (Q9UBU3) (ghre=growth) Key role in the motivation of feeding, but mechanisms still not characterized • Patients who have lost > 15% of their body weight by diet have significantly increased ghrelin levels and exaggerated peaks before meals compared to obese controls • GH • hunger
Ghrelin Ghrelin Kojima et al. Nature . 1999;402:656-60.
Vertical Sleeve Gastrectomy (VSG) in Ghrelin KO Mice Chambers et al., 2012 Gastroenterology
Vertical Sleeve Gastrectomy (VSG) in Ghrelin KO Mice Chambers et al., 2012 Gastroenterology Chambers et al., 2012 Gastroenterology
Vertical Sleeve Gastrectomy (VSG) in Ghrelin KO Mice Chambers et al., 2012 Gastroenterology
Important Hormones/Neurotransmittors: a description cholecystokinin (P06307) (chole=bile, cysto=pouch, kinin=move the bile bladder) Peptide hormone produced in the small intestine in response to feeding. It causes the release of digestive enzymes from the (exocrine) pancreas, bile from the galbladder and release of H + in parietal cells of the stomach. In the central nervous system it acts as an anorexigen (hunger suppressant). hunger
Important Hormones/Neurotransmittors: a description
Important Hormones/Neurotransmittors: a description
Important Hormones/Neurotransmittors: a description
Important Hormones/Neurotransmittors: a description Leptin (P41159) (leptos=thin) Peptide hormone released by adipose tissue in response to triglyceride loading. Leptin is the key hormone in energy balance regulation. Mice lacking the peptide or its receptor are obese. It acts as an anorexigen (hunger suppressant). But, leptin acts on many neurons and can gate food-related sensory input signals even at early stages of processing. hunger
Important Hormones/Neurotransmittors: a description Glucagon-like-peptide (GLP-1) Peptide hormone produced in the intestinal L cells of the distal small intestine. In the central nervous system it mediates vagal satiety signaling and conditioned taste avoidance. hunger
Hedonic Signals There are other parts of the brain involved in mediating the motivational (drive to eat), cognitive (learning and decision-making), and emotional components of food intake.
• Normal reward systems can lead to overeating in our modern, built environment of easily accessible and abundant food and food cues. • Food reward systems are essentially “go” systems and, while they can be diminished by hunger and satiety signals, they are normally never off.
• Experiences that evoked either extreme pleasure or complete disgust generate the most salient memories. • Representations contain a number of sensory attributes, including shape, color, taste, and flavor, as well as links to time, location, social context, cost, and reward expectation.
• Sensations & homeostatic signals must interact with brain reward systems to create pleasure (liking) and desire (wanting) – Sensory identification does not change based on internal need • Preferences & aversions are learned • Alliesthesia. Hunger & satiety states are enhanced or suppressed depending our internal state (fasted or fed)
Evaluative Processes • Learning Ameliorates illness (e.g., vitamin deficiency) - Provides motivation to try new foods. - Eating food that ameliorates illness causes food to be more liked .
Evaluative Processes • Learning Association with energy
Evaluative Processes Sal Salt-appet etite e • Help to explain eating components Senso sory-spe specif cific s ic satie iety Obtain nutrients ‘M ‘Medic icin inal’ l’ f food- preferenc erence e
Evaluative Processes • How do they influence the amount eaten? Taste-associated pleasure fluctuates according to internal state
Evaluative Processes • How do they influence the amount eaten? • Very hungry – pleasure starts higher so you eat more • Not hungry – pleasure starts lower so you stop eating sooner Pleasure of eating a food will gradually decrease with each bite (sensory specific satiety)
Evaluative Processes • How do they influence the amount eaten? • Pleasure may also make you • More likely to snack between more likely to eat due to an meals. external cue (e.g., smell of food, time of day, etc.) Meal Meal Meal Sna Snack Sna Snack Sna Snack
Sweet, fatty and salty foods…YUMMY
Bitter and sour… No thanks! • Bitter tastes are often associated with toxic alkaloids • Acidity of many sour substances indicate spoilage or un- ripeness
Experience • Basic taste sensations: sugars, starches, fats and proteins only allow rough assessment of caloric content, but inaccurate at informing us of caloric density. – But • Caloric consequences are NOT necessary for simple (but provocative) taste such as a sweet taste to maintain food-seeking behavior. • Nutritional value is not part of the sensory experience.
Taste perception or “palatability” • Palatability is neither a physical property of a food nor a fixed response in an individual… but rather an interaction between the food, the external context and internal signals for the current physiological state. • Virtually all acts of eating generate some degree of sensory pleasure.
FLAVOR • perceptual experience created by the synthesis of the simpler oral sensations tastes These senses combine in the mouth which convey a food’s odors textural, temperature and chemical irritants e.g. hot touch peppers.
Flavor • (Example: White chocolate is a poor substitute for true chocolate which differs only in cocoa (which consumed by itself is bitter)). But it adds complexity of flavor and aroma that has no intrinsic nutritional value to justify its appeal.
REWARD: Liking v. Wanting Liking v. Wanting • A model for understanding the motives (drives) to eat
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