This document discusses neuronal control of energy metabolism. It begins by outlining the motivations and interactions between homeostatic and hedonic mechanisms in regulating metabolism. Section 2 discusses how homeostatic and hedonic systems interact in the brain and body to control feeding behavior and energy balance. Section 3 describes how translational research integrates animal and human studies to further understand brain-body connections in metabolism. The document concludes by discussing various clinical applications for treating metabolic disorders.
Gluconeogenesis- Steps, Regulation and clinical significanceNamrata Chhabra
Gluconeogenesis- Thermodynamic barriers, substrates of gluconeogenesis, reciprocal regulation of glycolysis and gluconeogenesis, biological and clinical significance
Gluconeogenesis- Steps, Regulation and clinical significanceNamrata Chhabra
Gluconeogenesis- Thermodynamic barriers, substrates of gluconeogenesis, reciprocal regulation of glycolysis and gluconeogenesis, biological and clinical significance
This presentation includes information about secretion of glucagon, inhibitors, regulation of secretion, mechanism of action & actions of glucagon. It also includes ways to prevention of occurrence of hyperglycemia.
Metabolic Fate of Pyruvate and Cori cycle and Alanine cycle Cori & Alanine cy...Amany Elsayed
Metabolic Fate of Pyruvate and Cori cycle and Alanine cycle Cori & Alanine cycle and Lactate Dehydrogenase Deficiency (LDHA) and Malate aspartate shuttle (cycle) and Glycerol phosphate shuttle and Mitochondrial shuttle
1- metabolism of the brain (I) 2012-13.pdfMohamed Afifi
Cells of the nervous system: Neurons & Glial cells
▫ Neurons:
A neuron is Formed of:
Cell body:
▫ contains most of the cytoplasm & organelles
Cytoplasmic extensions:
▫ include an axon & many dendrites
Overvie
우리 몸은 체중, 체온, 혈압, 혈당, 전해질, 체액양 등을 일정하게 유지하는 항상성 조절 기능이 있다. 특히 특정 체중 조절점 (body weight set point)으로 체중을 일정하게 유지하는 기능은 비만의 병인에도 중요한 역할을 하고, 비만 치료에 있어서 문제가 되는 요요현상에서도 중요한 역할을 한다. 체중 조절점은 어떤 생물학적 기전으로 이루어지며, 잘 변하지 않는 체중 조절점이 어떤 기전으로 가변적이 될 수 있는지 알아보고자 한다. 또한, 이런 기전을 실제 비만클리닉에서 어떻게 적용할 수 있을지 살펴보고자 한다.
This presentation includes information about secretion of glucagon, inhibitors, regulation of secretion, mechanism of action & actions of glucagon. It also includes ways to prevention of occurrence of hyperglycemia.
Metabolic Fate of Pyruvate and Cori cycle and Alanine cycle Cori & Alanine cy...Amany Elsayed
Metabolic Fate of Pyruvate and Cori cycle and Alanine cycle Cori & Alanine cycle and Lactate Dehydrogenase Deficiency (LDHA) and Malate aspartate shuttle (cycle) and Glycerol phosphate shuttle and Mitochondrial shuttle
1- metabolism of the brain (I) 2012-13.pdfMohamed Afifi
Cells of the nervous system: Neurons & Glial cells
▫ Neurons:
A neuron is Formed of:
Cell body:
▫ contains most of the cytoplasm & organelles
Cytoplasmic extensions:
▫ include an axon & many dendrites
Overvie
우리 몸은 체중, 체온, 혈압, 혈당, 전해질, 체액양 등을 일정하게 유지하는 항상성 조절 기능이 있다. 특히 특정 체중 조절점 (body weight set point)으로 체중을 일정하게 유지하는 기능은 비만의 병인에도 중요한 역할을 하고, 비만 치료에 있어서 문제가 되는 요요현상에서도 중요한 역할을 한다. 체중 조절점은 어떤 생물학적 기전으로 이루어지며, 잘 변하지 않는 체중 조절점이 어떤 기전으로 가변적이 될 수 있는지 알아보고자 한다. 또한, 이런 기전을 실제 비만클리닉에서 어떻게 적용할 수 있을지 살펴보고자 한다.
My recent introduction talk for the Nutrigenomics Masterclass 2011in Wageningen (The Netherlands):
How to use Nutrigenomics & molecular nutrition? From challenges to solutions
By:Nader Al-assadi
Taiz university
Definition of weight loss:
Clinically important weight loss is defined as the loss of 10 pounds (4.5 kg) or >5% of one’s body weight over a period of 6–12 months.
Weight loss can be divided into 2 categories: involuntary or voluntary.
-1 Involuntary weight loss is a manifestation of cachexia associated with many disease states.
2- Voluntary weight loss, in the form of healthy dieting, is common among men and women. However, signifcant voluntary weight loss can herald a psychiatric illness such as an eating disorder, particularly among women.
K E Y T E R M S:
Anorexia Loss of the desire to eat.
Anorexia nervosa4 Intense fear of gaining weight and refusal to maintain weight at or above a minimally appropriate weight for height and age.
Bulimia nervosa4 Recurrent episodes of binge eating followed by recurrent compensatory behavior to prevent weight gain (ie, laxative abuse and self-induced vomiting).
Cachexia General muscle and/or fat wasting with malnutrition usually associated with chronic disease.
Involuntary weight loss The unintended loss of weight; sometimes not reported by the patient and only noted upon chart review.
Malnutrition Poor nutrition due to inadequate or unbalanced intake of nutrients or their impaired utilization.
Voluntary weight loss The conscious effort to lose weight; frequently not a complaint among those with eating disorders.
Anti-Obesity Pharmacotherapy: Where are we now? Where are we going?InsideScientific
Obesity is a treatable chronic disease. With nearly 2 billion individuals worldwide classified as being overweight and 650 million as having obesity, it is critical to optimize implementation of existing treatment interventions and develop novel therapies to mitigate the obesity pandemic. Anti-obesity medications are one of the essential tools in our medical toolbox to help patients achieve their health and weight goals.
In this webinar, Dr. Jastreboff discusses current use of anti-obesity pharmacotherapy, mechanisms involved, and agents in various stages of development with considerations for next steps. The presentation aims to inspire development of innovative therapeutics while optimizing use of existing agents to address the urgent need to effectively and sustainably treat millions of individuals with obesity around the world.
Key Topics Include:
- Understand the role of anti-obesity pharmacotherapy in the treatment of obesity
- Describe current anti-obesity pharmacotherapy
- Discuss anti-obesity medications under development
Obesity PHR Big Data - Research and Clinical ApplicationsHyung Jin Choi
1. Obesity
2. Obesity Big Data
1) Genetics
2) Environment
3) Electrical Health Record
4) Imaging
5) Mobile/Sensor
6) National Health Record
7) Social Network Service
3. Research
4. Clinical Application
To learn more and watch the webinar, visit:
https://insidescientific.com/webinar/brain-circuits-driving-appetite-obesity-2020
In many western countries, nearly a quarter of us meet the criteria for clinical obesity and more than half of us are overweight. This is a medical concern because obesity is a serious risk factor for many major chronic illnesses, such as heart disease, type 2 diabetes and cancer, and as a result, obesity is associated with reduced lifespan by almost a decade. The rapid escalation in the prevalence of obesity and the paucity of obesity medications underscores the necessity of an understanding of the basic neurobiology underlying body weight.
During this webinar, Professor Heisler will discuss brain circuits that are the main known controllers of body weight, such as those activated by the adipocyte hormone leptin. She will review how our genes impact our waistline and will discuss crucial genes such as those in the melanocortin system. Professor Heisler will discuss how obesity medications capitalize on this basic neurobiology to promote satiety, reduce hunger and decrease body weight.
Key discussion topics include:
– Gut to brain communication
– Key brain chemicals mediating satiety
– Key brain chemicals controlling hunger
1. What is Stress?
2. Mechanism
Neuro-Anatomy of Stress
Neuro-Endocrine of Stress
Inflammation and Stress
3. Stress and Disease
Stress and Food Addiction
4. Stress and Central Regulation of Metabolism
Biomedical big data and research clinical application for obesityHyung Jin Choi
1. What is Biomedical Big Data?
2. Biomedical Big Data
1) Genetic Data
2) Electrical Health Records
3) National Healthcare Data
4) Medical Images
5) Sensor/Mobile Data
6) Data Integration
3. Biomedical Big Data + Artificial Intelligence
4. Research/Clinical Application for Obesity
The Present and Future of Personal Health Record and Artificial Intelligence ...Hyung Jin Choi
1. Why Personal Health Record and Artificial Intelligence ?
2. Obesity Example
3. Personal Health Record
1) Genetic Data
2) Electrical Health Records
3) National Healthcare Data
4) Medical Images
5) Sensor/Mobile Data
6) Data Integration
4. PHR+AI Applications
- 의료 빅데이터 - 개념 입문과 임상의사가 할 수 있는 일
빅데이터 개념 입문과
의료와 관계된 빅데이터 종류와 활용 방법
진료와 연구에 활용할 수 있는 방법을
임상의사의 관점에서 다루었습니다.
1. What is Big Data?
2. Healthcare Big Data
1) Electrical Health Records (EHR) Structured/Unstructured Data
2) Medical Images
3) National Healthcare Data
4) Behavior/Sensor Data
5) Genetic Data
3. Clinical and Research Applications
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Antimicrobial stewardship to prevent antimicrobial resistanceGovindRankawat1
India is among the nations with the highest burden of bacterial infections.
India is one of the largest consumers of antibiotics worldwide.
India carries one of the largest burdens of drug‑resistant pathogens worldwide.
Highest burden of multidrug‑resistant tuberculosis,
Alarmingly high resistance among Gram‑negative and Gram‑positive bacteria even to newer antimicrobials such as carbapenems.
NDM‑1 ( New Delhi Metallo Beta lactamase 1, an enzyme which inactivates majority of Beta lactam antibiotics including carbapenems) was reported in 2008
Top Effective Soaps for Fungal Skin Infections in India
Neuronal Control of Energy Metabolism
1. Neuronal Control of
Energy Metabolism
Hyung Jin Choi
Functional Neuroanatomy of Metabolism Regulation (FNMR) Lab, Department of Anatomy,
Seoul National University College of Medicine 1
Animal, Human and Cadaver Research
2. Contents
1. Motivation: What Drives Our Mind and Body?
2. Homeostatic/Hedonic Interactions
3. Brain-Body Connections
4. Translational Research
5. Clinical Applications
2
3. Contents
1. Motivation: What Drives Our Mind and Body?
2. Homeostatic/Hedonic Interactions
3. Brain-Body Connections
4. Translational Research
5. Clinical Applications
3
5. 고통을 회피하는 것과 쾌락을 원하는 것은
모든 행위의 두 가지 시동장치이다.
Man can do what he wills,
but he cannot will what he wills.
—Arthur Schopenhauer,
On the Freedom of the Will
5
고통을 회피하는 것과 쾌락을 원하는 것은
모든 행위의 두 가지 시동장치이다.
- 베르나르 베르베르 “뇌”
6. Pleasure Pain
Satiety
Libido
Hunger
Approach Avoid
Craving Fear
Anxiety
Appetite
Comfort Physical
Pain
Loneliness
Social Defeat
Love
Social Success
Fear of
starvation
Mania Depression
Anhedonia
Impulsive
Energy
Reproduction
Safety
Addiction Phobia
6
7. 7
2011 Nature. Functional identification of an aggression locus in the mouse hypothalamus.
Male Male Male Female
Male Female +Optogenetic Stim. Male Glove +Optogenetic Stim.
13. 2012 JCEM Regulation of food intake, energy balance, and body fat mass- implications for the pathogenesis and treatment of obesity
Appetite
Appetite
Homeostatic Regulation of
Body Fat Mass
14. The Lipostatic Model of
Body Fat Regulation
14
2011 Set points, settling points and some alternative models- theoretical options to understand how genes and environments combine to regulate body adiposity
15. 2012 Nature Medicine Shedding pounds after going under the knife
↑Agrp
↑NPY
↓POMC
↓ Agrp
↓ NPY
↑ POMC
16. 16
2016 TEM Opposite Regulation of Ghrelin and Glucagon-like Peptide-1 by Metabolite G-Protein-Coupled Receptors
Hunger Satiety
19. Ghrelin
- Before Meals↑
- After Weight Loss↑
2002 NEJM Plasma Ghrelin Levels after Diet-
Induced Weight Loss or Gastric Bypass Surgery
20. Responses of Leptin to
Short-term Fasting and Refeeding
20
1996 Diabetes. Responses of leptin to short-term fasting and refeeding in humans- a link with ketogenesis but not ketones
21. 2011 NEJM Long-term persistence of hormonal adaptations to weight loss.
N=50
22. 1995 NEJM Changes in energy expenditure resulting from altered body weight
23. 1995 NEJM Changes in energy expenditure resulting from altered body weight
24. Weight Change Induced
Energy Expenditure Change
1995 NEJM Changes in energy expenditure resulting from altered body weight
25. ~ 100 kcal/d
Per kg BW/loss
2016 Obesity. How Strongly Does Appetite Counter Weight Loss Quantification of the Feedback Control of Human Energy Intake
SGLT2 inhibitor
(Canagliflozin)
26. Physiological Needs Influence Behavior
through Discrete Hypothalamic Circuits
2013 Neuron. Hypothalamic Survival Circuits- Blueprints for Purposive Behaviors
26
27. 27
2013 Science. The inhibitory circuit architecture of the lateral hypothalamus orchestrates feeding
28. 2008 Obesity. Central and Peripheral Regulation of Food Intake and Physical Activity
29. 29
2014 J Endocrinol. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance
30. Energy Set Point
Synaptic Plasticity
30
2013 Trends in Neuroscience. Hypothalamic control of energy balance- insights into the role of synaptic plasticity
31. Mutations in the Leptin-Melanocortin Pathway in Humans
31
2015 Food reward system- current perspectives and future research needs
32. Growth Charts for Two
Children with MC4R Deficiency
32
2003 NEJM Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
33. MC4R Mutation
33
2003 NEJM Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
9-year-old boy
homozygous for a mutation in MC4R
His 16-year-old brother
34. Energy Intake in
MC4R Deficiency and Leptin Deficiency
34
2003 NEJM Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
35. 2016 NEJM Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist
MC4R Agonist for POMC Mutation Patient
38. Areas of the Human Brain Activated
in Response to Palatable Food or
Food-Associated Cues
38
2011 Neuron. Reward mechanisms in obesity- new insights and future
39. Important Brain Areas Involved in the Regulation of
Eating Behaviour and Body Weight
39
2016 Lancet Diabetes and Endocrinology. Functional neuroimaging in obesity and the potential for development of novel treatments
40. 40
2014 JCEM Obesity-Associated Melanocortin-4 Receptor Mutations Are Associated With Changes in the Brain Response to Food Cues
Activation of Dorsal and Ventral Striatum
in MC4R Deficiency Patients
Response to appetizing foods compared to
non-food objects
N=8 N=10 N=8
41.
42. Stress and Food Intake
2009 Trends in Endocrinology and Metabolism- Stress-induced obesity and the emotional nervous system
43. 2013 Biological Psychiatry. Stress as a Common Risk Factor for Obesity and Addiction
Increased limbic and striatal reactivity to stress and food cues in obese individuals
44. Model of Insulin Resistance, Regional Brain
Activation, and Food Craving in Obese Individuals
2012 Diabetes Care. Neural Correlates of Stress- and Food- Cue-Induced Food Craving In Obesity
Vicious cycle driving weight gain
45.
46. “Obesity and drug addiction may share common hedonic mechanisms”
2011 Neuron. Reward mechanisms in obesity- new insights and future directions
47. 좋아함(Liking) 과 원함
(Wanting)
• 좋아함 “Liking” (쾌감 효과)
• 원함 “Wanting” (유인적 동기부여)
• 학습 Learning (연관만들기, 예측)
• 좋아함 없는 원함 “Wanting”
without “liking”
• 약물중독의 공통적 기전
2010 Brain Research- The tempted brain eats- Pleasure and desire circuits in obesity and eating disorders
57. Tissue Specific Expression
of BMI Regulating Genes
2015 Nature. Genetic studies of body mass index yield new insights for obesity biology
- Hypothalamus, Pituitary gland
(appetite regulation)
- Hippocampus, Limbic system
(learning, cognition, emotion,
memory)
61. 2017 Nature. (News and Views) Physiology- Gut feeling for food choice
Bariatric Surgery and Pleasure for Food
62. 2015 TEM Distinctive striatal dopamine signaling after dieting and gastric bypass
Homeostatic Reward and Hedonic
Reward
Hedonic Reward
Homeostatic Reward
Hedonic Reward
Homeostatic Reward
Hedonic Reward
Homeostatic Reward
Hedonic Reward
Homeostatic Reward
63. Homeostatic
Drive to Eat
Hedonic
Drive to Eat
Homeostatic
Energy Expenditure
(Resting Energy
Expenditure)
Hedonic Reward Driven
Energy Expenditure
(Exercise Energy
Expenditure)
HomeostaticHedonic
2013 Principles of Neural Science. Fifth Edition. Kandel et al.
64. Homeostatic
Drive to Eat
Hedonic
Drive to Eat
Homeostatic
Energy Expenditure
(Resting Energy
Expenditure)
Hedonic Reward Driven
Energy Expenditure
(Exercise Energy
Expenditure)
HomeostaticHedonic
2013 Principles of Neural Science. Fifth Edition. Kandel et al.
Slow Adaptation of
Set Point to New Level
(Network Change,
Synaptic plasticity?)
Weight Gain
65. Determination of the Settling
Point for Food Intake
Food
Availability
Palatability
Leptin Resistance↑Adiposity↑ Leptin↑
2010 Trends in Endocrinology and Metabolism- Obesity and leptin resistance- distinguishing cause from effect
New Set Point
66. 66
Set Point Energy Storage Temperature Glucose Blood Pressure
Normal Normal Weight Normal BT Normal Glucose Normal BP
Physiologic
Alteration
Pregnancy
Hibernation
Hibernation Exercise?
Acute Stress?
Exercise?
Acute Stress?
Disease Obesity Febrile
Disease
Diabetes? Hypertension?
Set Point Alteration and Diseases
67. Contents
1. Motivation: What Drives Our Mind and Body?
2. Homeostatic/Hedonic Interactions
3. Brain-Body Connections
4.Translational Research
5.Clinical Applications
67
Pancreas
Gut
Liver
Fat
68. 68
2013 Trends in Neuroscience. Hypertension in obesity- is leptin the culprit
70. 70
2010 BBA The role of the autonomic nervous liver innervation in the control of energy metabolism
71. 2015 TEM. Brain glucose sensing in homeostatic and hedonic regulation.
72. 2015 TEM. Brain glucose sensing in homeostatic and hedonic regulation.
73. 2015 NRGH Towards a systems view of IBS
Stress-Brain-Gut-Microbiota Axis
73
74. 74
2016 Cell. Sensory Neurons that Detect Stretch and Nutrients in the Digestive System
Imaging Single Neuron Responses in
Vagal Ganglia In Vivo
GLP1R GPR65
75. 2016 Cell. Sensory Neurons that Detect Stretch and Nutrients in the Digestive System
76. Contents
1. Motivation: What Drives Our Mind and Body?
2. Homeostatic Mechanism
3. Hedonic Mechanism
4. Homeostatic/Hedonic Interactions
5. Brain-Body Connections
6.Translational Research
7.Clinical Applications
76
77. Translational Research
Animal + Human Research
Animal
Genetics
Human
Data Science
Surgical Model
Physiology Study
College of Medicine
Imaging
Biobank
Clinical Insight
Pharmacological Model
Genetic Model
Clinical Trial
Mechanistic Insight
Tools
Understanding of
Biology and Mechanism
Understanding of
Human Metabolism and
Disease
Brain Imaging
Cadaver Study
78. Stereotaxic Brain Modulation
Stereotaxic Surgery
Pharmacologic Treatment
Genetic Modification
(Cre/flox, CRISP)
Optogenetics/Chemogenetics
Genetic Profiling
1. Animal Study
78
79. Human Brain Mapping for
Metabolism Regulation
Paraventricular Nucleus (PVN)
Lateral Hypothalamus Area (LHA)
Arcuate Nucleus (ARC)
Cadaver Donor
2. Cadaver Study
Immunofluorescence
Immunohistochemistry
Micro+Macro Functional Mapping
79
85. 85(2014) Diabetes. GLP-1 Agonism Stimulates Brown Adipose Tissue Thermogenesis and Browning Through Hypothalamic AMPK
2016 Trends in Molecular Medicine. Reappraisal of GIP Pharmacology for Metabolic Diseases
1. GLP-1 on Brain-Gut Axis
86. 1. GLP-1 on Brain-Gut Axis
2014 JCI. Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight
90. Human Brain GLP-1R Mapping
GFAP+GLP-1R
Orthogonal projection
GFAP+GLP-1R
1. GLP-1 on Brain-Gut Axis
91. 91
1. GLP-1 on Brain-Gut Axis
No effect in lean individuals
In obese subjects, exenatide infusion caused an increase in
the hypothalamic fMRI signal but had no effect in lean
individuals
2016 Diabetes Care. Discordance Between Central (Brain) and Pancreatic Action of Exenatide in Lean and Obese Subjects
GLP-1 human fMRI study
GLP-1 analog
92. GLP-1 fMRI Human Study
3
+
Food presentation
max 4sec
Feedback
1sec
Fixation
1~10sec
Time
GLP-1 agonist or
placebo
Visual task
(food image)
Blood test/survey
Resting
T1 structure/DTI 17 min
12 min
12 min
Survey
Crossover, placebo-controlled trial
Subjects
1) Lean T2DM BMI<23 (n=15)
2) Obese T2DM BMI>26 (n=15)
Survey
Buffet
1. GLP-1 on Brain-Gut Axis
96. Optogenetic and Chemogenetic
Modulation of Neuronal Activity
96
2016 Cell. Sensory Neurons that Detect Stretch and Nutrients in the Digestive System
2. Chemogenetic Activation of Brain-Body Connections
97. 97
Target specific cre mouse
Stereotaxic Injection of Chemogenetic Virus
Expression of
Chemogenetic
Receptor
Specific Drug (CNO)
Intraperitoneal Injection
Specific Neuron Modulation Using
Chemogenetics
2. Chemogenetic Activation of Brain-Body Connections
99. Effect of Parasympathetic Activation on
Food Intake and Glucose Metabolism
99
Gluconeogenesis
Insulin Secretion
Appetite
Gut
?
2. Chemogenetic Activation of Brain-Body Connections
104. Mouse and Human Nodose Ganglion
104
Merge
MergeNPY 1:250
ChAT 1:1000
DAPI
SNU FNMR, unpublished
3. Visualization of Brain-Body Connections
105. Brain CLARITY
• 신경 사이의 연결 네트워크 분석 가능
• 3차원적 신경 구조 분석 가능
105Human hypothalamus
2차원 단면 이미징 3차원 투명화 신경 연결 분석
(Nature Biotechnology, 2016)(JCEM, 2015)
4. Human Brain Functional Mapping
106. 106
DAPI – blue, POMC – green, AgRP - red
Schematic Illustration of Study Goal
ARH
PVH
LHA
Kwanghun Chung, Nature Biotechnology. 2016
Neuronal Network Analysis Using CLARITY
3mm tracing
4. Human Brain Functional Mapping
Neuroanatomy and Network of
Metabolism Regulation
Geographic Functional Mapping
Micro-Meso Neural Circuit
Synaptic Plasticity (Obesity, DM)
114. Contents
1. Motivation: What Drives Our Mind and Body?
2. Homeostatic/Hedonic Interactions
3. Brain-Body Connections
4.Translational Research
5.Clinical Applications
114
115. 2015 Cell. Neural Control of Energy Balance- Translating Circuits to Therapies
Selected
Therapeutic
Options for
Treating
Obesity and
Diabetes by
Targeting
the Brain
120. 2015 Cell. Neural Control of Energy Balance- Translating Circuits to Therapies
Transcranial Direct Current Stimulation (tDCS) VBLOC: vagal blocking therapy
2015 Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and
2015 FDA approved
122. tDCS Decreases Food Craving
Real tDCS
Sham tDCS
Real tDCS
Sham tDCS
Craving Trouble resisting
2011 Appetite. Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces
food cravings and increases the self-reported ability to resist food in adults with frequent food craving
122
5. tDCS neuromodulation for Obesity
123. Long-term tDCS Treatment
Decreases Food Intake
2014 AJCN Repetitive electric brain stimulation reduces food intake in humans
123
5. tDCS neuromodulation for Obesity
124. Experimental Protocol
3
+
Food presentation
max 4sec
Feedback
1sec
Fixation
1~10sec
Time
tDCS or sham
stimulation
Visual task
(food image
ratings)
Blood test/survey
Resting MRI
T1 structure MRI
5-6min
7min
5-6min
20min
Blood test/survey
124
1. Single Treatment Study
126. Green Lines: orexigenic pathways
Red lines: dopaminergic pathways
2013 The contribution of brain reward circuits to the obesity epidemic
2014 Obesity – A neuropsychological disease- Systematic review and neuropsychological mode
A, amygdala;
H, hypothalamus;
NA, nucleus accumbens,
PFC, prefrontal cortex;
VTA, ventral tegmental area
126
tDCS Neuromodulation Controls
Feeding Behavior via
Food Reward Activity and Connectivity
Neuromodulation Brain Activity Feeding Behavior
Brain Connectivity
5. tDCS neuromodulation for Obesity
127. Research Projects
1. GLP-1 on Brain-Gut Axis
2. Chemogenetic Activation of Brain-Body
Connections
3. Visualization of Brain-Body Connections
4. Human Brain Functional Mapping
5. tDCS neuromodulation for Obesity
127
128. 2008 Obesity Central and Peripheral Regulation of Food Intake and Physical Activity
Human Brain
129. 2008 Obesity Central and Peripheral Regulation of Food Intake and Physical Activity
Human Brain
CLARITY
Chemogenetics