A Regulatory Perspective

Fourth Edition

Keith N. Frayn

Emeritus Professor of Human Metabolism
Radcliffe Department of Medicine
University of Oxford
Oxford, UK

and

Rhys D. Evans

Reader in Metabolic Biochemistry
Department of Physiology, Anatomy and Genetics
University of Oxford
Oxford, UK
and

Consultant in Anaesthetics and Intensive Care Medicine
Oxford University Hospitals NHS Trust
John Radcliffe Hospital
Oxford, UK

Edition History
Portland Press (1e, 1996); Blackwell Science (2e, 2003); Wiley-Blackwell (3e, 2010).
(Editions 1 to 3 published under the title of Metabolic Regulation: A Human Perspective.)

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Library of Congress Cataloging-in-Publication Data
Names: Frayn, K. N. (Keith N.), author. | Evans, Rhys D. (Rhys David), author.
Title: Human metabolism : a regulatory perspective / Keith N. Frayn and Rhys D. Evans.
Other titles: Metabolic regulation
Description: Fourth edition. | Hoboken, NJ : Wiley-Blackwell, 2019. | Preceded by Metabolic regulation / Keith N. Frayn. 3rd ed. 2010. | Includes bibliographical references and index. |
Identifiers: LCCN 2018039797 (print) | LCCN 2018041323 (ebook) | ISBN 9781119331445 (Adobe PDF) | ISBN 9781119331469 (ePub) | ISBN 9781119331438 (paperback)
Subjects: | MESH: Metabolism—physiology | Metabolic Diseases—physiopathology | Metabolic Networks and Pathways—physiology
Classification: LCC QP171 (ebook) | LCC QP171 (print) | NLM QU 120 | DDC 612.3/9—dc23
LC record available at https://lccn.loc.gov/2018039797

Cover images: courtesy of Keith Frayn and Rhys Evans, © John Wiley & Sons, Inc.
Cover design by Wiley

CONTENTS

Cover

Preface

Abbreviations

About the companion website

CHAPTER 1 The underlying principles of human metabolism

1.1 Metabolism in perspective
1.2 The chemistry of food – and of bodies
1.3 General overview of metabolism
Note

CHAPTER 2 Cellular aspects of metabolic regulation

2.1 What is metabolic regulation?
2.2 What makes one tissue different from another?
2.3 Rapid changes in metabolic flux and how they are achieved
2.4 Longer-term control of metabolic pathways
Note

CHAPTER 3 Coordination of metabolism in the whole body

3.1 Metabolic regulation involves communication between tissues
3.2 What connects the tissues?
3.3 Hormones and their receptors
3.4 Hormones and short-term control of enzyme activity
3.5 Hormones and longer-term control of enzyme activity

CHAPTER 4 Digestion and intestinal absorption

4.1 The strategy of digestion
4.2 Stages of digestion
4.3 Absorption from the small intestine
4.4 The large intestine
Note

CHAPTER 5 Metabolic specialisation of organs and tissues

5.1 The liver
5.2 Adipose tissue
5.3 Skeletal muscle
5.4 The heart
5.5 The kidneys
5.6 The brain
5.7 The endothelium – a large organ distributed throughout the body
5.8 Enterocytes
5.9 Cells of the immune system
Notes

CHAPTER 6 Communication systems

6.1 Communication systems
6.2 Hormones important in metabolic regulation
6.3 The nervous system and metabolism
Note

CHAPTER 7 Integration of carbohydrate, fat and protein metabolism in normal daily life

7.1 The body’s fuel stores
7.2 Carbohydrate metabolism
7.3 Lipid metabolism
7.4 Amino acid and protein metabolism
7.5 Links between carbohydrate, lipid, and amino acid metabolism
7.6 Blood flow and the integration of metabolism
7.7 An integrated overview of metabolism: a metabolic diary
7.8 Metabolic control in a physiological setting
Notes

CHAPTER 8 Metabolic challenges: Coping with some extreme physiological situations

8.1 Situations in which metabolism is significantly altered from its normal pattern
8.2 Exercise
8.3 Growth and development
Notes

CHAPTER 9 Metabolic challenges: Coping with some pathological situations

Pathological challenges to metabolism
9.1 Starvation
9.2 The period of adapted starvation
9.3 Pathological stress: the metabolic response to tissue injury and the effects of inflammation, infection and trauma
9.4 Cancer metabolism

CHAPTER 10 Lipoprotein metabolism and atherosclerosis

10.1 Introduction to lipoprotein metabolism
10.2 Outline of the pathways of lipoprotein metabolism
10.3 Regulation of lipoprotein metabolism
10.4 Disturbances of lipoprotein metabolism

CHAPTER 11 Energy balance and body weight regulation

11.1 Energy balance and body weight
11.2 Energy balance
11.3 Conditions of low body weight
11.4 Treatment of obesity
Note

CHAPTER 12 Diabetes mellitus

12.1 Different types of diabetes
12.2 Clinical features of diabetes
12.3 Metabolic alterations in diabetes mellitus
12.4 Treatment of diabetes mellitus
12.5 The longer-term complications of diabetes
12.6 Prevention of diabetes
Note

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1
Table 1.2

Chapter 2

Table 2.2-1
Table 2.1
Table 2.2
Table 2.3
Table 2.4
Table 2.5
Table 2.6

Chapter 3

Table 3.1
Table 3.2

Chapter 4

Table 4.1
Table 4.2
Table 4.3

Chapter 5

Table 5.1
Table 5.2
Table 5.3

Chapter 6

Table 6.1
Table 6.2
Table 6.3

Chapter 7

Table 7.1
Table 7.2
Table 7.3

Chapter 8

Table 8.1
Table 8.2
Table 8.3
Table 8.4
Table 8.5

Chapter 9

Table 9.1
Table 9.2

Chapter 10

Table 10.1
Table 10.2

Chapter 11

Table 11.1
Table 11.2
Table 11.3
Table 11.4

Chapter 12

Table 12.1
Table 12.2
Table 12.3

List of Illustrations

Chapter 1

Figure 1.1 Rates of energy intake and output for a motor vehicle. The rate of intake (top ...
Figure 1.2 Rates of energy intake and output for a person during a typical day. The rate o...
Figure 1.3 (a) Three-dimensional structure of the methane molecule and (b) the molecular s...
Figure 1.4 Chemical structures of some lipids. A typical saturated fatty acid (palmitic ac...
Figure 1.5 Structure of biological membranes in mammalian cells. Cell membranes and intrac...
Figure 1.6 Cholesterol and a typical cholesteryl ester (cholesteryl oleate). In the struct...
Figure 1.7 Some simple sugars and disaccharides. Glucose and fructose are shown in their ‘...
Figure 1.8 Structure of glycogen. Left-hand side: each circle in the upper diagram represe...
Figure 1.9 Pictures of the molecular shapes of different fatty acids. (a) saturated fatty ...
Figure 1.10 Comparison of fat and carbohydrate as fuel sources. Raw potatoes (right) are hy...
Figure 1.11 Structure of an amino acid. At physiological pH (7.4) the carboxyl group is ion...
Figure 1.12 Catabolism and anabolism.
Figure 1.13 Overall metabolic energy flux. The three energy groups (fats, carbohydrates, pr...
Figure 1.14 Pathways of glucose metabolism inside the cell. The pathways of glucose (carboh...
Figure 1.15 Lactate and ethanol metabolism. Glycolysis produces NADH from NAD⁺. (a) In aero...
Figure 1.16 Pathways of lipid metabolism in the cell. Synthesis of fatty acids from acetyl-...
Figure 1.17 Lipid metabolism pathways. Importance of lipolysis and esterification pathways ...
Figure 1.18 Parallel between soap manufacture (saponification) and fat mobilisation. In sap...
Figure 1.19 Metabolism of amino acids. To be metabolised, amino acids must first be deamina...
Figure 1.20 Transamination reactions. Transamination involves the transfer of an amino grou...
Figure 1.21 Deamination of amino acids. By linking transamination reactions to oxidative de...
Figure 1.22 Urea cycle. One nitrogen atom enters the cycle as an ammonium ion from glutamat...
Figure 1.23 Metabolism of the carbon skeletons of amino acids following their deamination. ...

Chapter 2

Figure 2.2.1
Figure 2.1 Sodium-linked active transport. By co-transport with Na⁺ ions, substance X may ...
Figure 2.2 GLUT4 recruitment to the cell membrane. There is an intracellular pool of GLUT4...
Figure 2.3 Different methods for achieving changes in metabolic flux within a cell. A hypo...
Figure 2.5.1
Figure 2.4 Different stages at which the amount of a protein present in a cell may be cont...
Figure 2.5 Operation of the circadian clock at a cellular level. The proteins CLOCK (circa...
Figure 2.6 Glucose control of expression of lipogenic genes. Glucose increases gene expres...
Figure 2.7 The PPAR system. The ligand for the PPAR (a fatty acid, or a fatty acid derivat...
Figure 2.8 The SREBP system. The full-length SREBP protein is located in the endoplasmic r...

Chapter 3

Figure 3.1 The circulatory system. Oxygenated blood from the lungs returns in the pulmonar...
Figure 3.2 Diffusion of chemical substances through the interstitial fluid. A typical tiss...
Figure 3.3.1 Synthesis and breakdown of cAMP
Figure 3.3.2 PI3K, phosphatidylinositol-3-kinase; PLC, phospholipase C....
Figure 3.4.1 Signal chain for regulation of many metabolic processes by insulin. Insulin bin...
Figure 3.4.2 Signal chain for stimulation of glycogen breakdown by adrenaline (or noradrenal...
Figure 3.4.3 Signal chain for control of hormone-sensitive lipase (HSL) in adipocytes. HSL i...

Chapter 4

Figure 4.1 Anatomy of the digestive tract and associated organs.
Figure 4.2 Control of gastric acid secretion. Plus signs indicate stimulation or activatio...
Figure 4.3 Structure of a villus of the small intestine. One of the absorptive cells (ente...
Figure 4.4 Vessels carrying the products of digestion away from the small intestine. Subst...
Figure 4.2.1
Figure 4.5 Lipid digestion and absorption in the small intestine. Fatty acids and choleste...
Figure 4.6 Hormonal regulation of the secretion of digestive juices. Gastrin stimulates hy...
Figure 4.7 Absorption of monosaccharides from the intestine. Monosaccharides enter the ent...
Figure 4.8 Esterification pathways for the formation of triacylglycerol. The monoacylglyce...
Figure 4.9 Cholesterol absorption. Niemann-Pick C1-like protein-1 (NPC1L1), expressed at t...

Chapter 5

Figure 5.1 Arrangement of hepatocytes in liver lobules. In a cross-section of the liver, t...
Figure 5.2 Outline of glucose metabolism and its hormonal regulation in the liver. Dashed ...
Figure 5.1.1
Figure 5.2.1
Figure 5.3.1 Pathways around pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase...
Figure 5.3 The pentose phosphate pathway and its links with lipogenesis. G 6-P, glucose 6-...
Figure 5.4 Overview of fatty acid metabolism in the liver. Fatty acids cross the hepatocyt...
Figure 5.5 The pathway of ketone body formation from acetyl-CoA (ketogenesis). This is loc...
Figure 5.4.1
Figure 5.6 Outline of amino acid metabolism in the liver. Liver contains the enzymes of gl...
Figure 5.7 Appearance of brown and white adipose tissue. Left, white adipose tissue under ...
Figure 5.8 Overview of fatty acid and glucose metabolism in white adipose tissue. The body...
Figure 5.9 The action of lipoprotein lipase in white adipose tissue. Top panel: Lipoprotei...
Figure 5.10 The intracellular pathway of lipolysis in adipocytes. Triacylglycerol (TAG) in ...
Figure 5.11 Suppression of fat mobilisation by insulin. Top panel: Insulin restrains fat mo...
Figure 5.12 Uncoupling of respiration in brown adipose tissue (and potentially other tissue...
Figure 5.13 Human brown adipose tissue depots. Brown adipose tissue (BAT) depots around the...
Figure 5.14 Structural organisation of skeletal muscle. One cell is a muscle fibre. The who...
Figure 5.15 The creatine kinase reaction in muscle. The reaction is referred to as the Lohm...
Figure 5.16 Fibre-type composition of leg muscles in athletes. Different types of muscle fi...
Figure 5.17 ATP generation in skeletal muscle. Only major pathways are shown: each arrow ma...
Figure 5.7.1
Figure 5.18 (a) Section of kidney and (b) schematic view of energy metabolism in different ...
Figure 5.19 The endothelium, a smooth single-celled lining of blood vessels.
Figure 5.20 Generation of nitric oxide (NO) from arginine in endothelial cells leads to rel...
Figure 5.21 Amino acid metabolism in enterocytes. In the fed state the enterocytes oxidise ...

Chapter 6

Figure 6.1 The location of endocrine glands involved in energy metabolism. The thymus is s...
Figure 6.2 Islets of Langerhans in the pancreas. The pancreatic tissue has been immunostai...
Figure 6.3 Synthesis of insulin. Insulin is first synthesised as one long polypeptide, pre...
Figure 6.4 Glucose stimulation of insulin secretion in the pancreatic β-cell. Glucose ente...
Figure 6.5 Dose–response curve for the effects of glucose concentration on the secretion o...
Figure 6.6 Pituitary hormones and their target organs.
Figure 6.7 The anatomy of the thyroid gland.
Figure 6.8 Biosynthesis of the thyroid hormones. Thyroxine (T₄) and triiodothyronine (T₃) ...
Figure 6.9 The anatomy of the adrenal glands.
Figure 6.10 Biosynthesis of the catecholamines. Noradrenaline is a neurotransmitter, releas...
Figure 6.11 Propranolol (a β-adrenergic blocker) inhibits lipolysis in response to exercise...
Figure 6.12 The leptin system and regulation of fat stores. Leptin is produced in, and secr...
Figure 6.13 The idea of ‘incretins’ (gut-derived hormones that augment insulin secretion). ...
Figure 6.14 Basic structure of a nerve cell (neurone).
Figure 6.15 The structures of two important neurotransmitters, acetylcholine, and noradrena...
Figure 6.1.1
Figure 6.2.1
Figure 6.16 The human brain and its main components.
Figure 6.17 The neuromuscular junction.
Figure 6.18 Types of neurotransmission in the central and peripheral nervous systems. ACh, ...
Figure 6.19 Plasma glucagon, adrenaline, and noradrenaline concentrations in response to ra...

Chapter 7

Figure 7.1 Relative constancy of blood glucose concentrations during a typical day, compar...
Figure 7.2 An analogy for metabolic regulation. The temperature in a thermostatically cont...
Figure 7.3 The pattern of glucose metabolism after an overnight fast. The numbers are appr...
Figure 7.4 Concentrations of insulin, glucose, and lactate in blood after an overnight fas...
Figure 7.5 Rates of glucose release from liver, from exogenous (dietary) and endogenous (g...
Figure 7.6 Increases in liver and skeletal muscle glycogen after a single meal in normal s...
Figure 7.7 The pattern of glucose metabolism after a carbohydrate breakfast. The direct pa...
Figure 7.8 Plasma non-esterified fatty acid (NEFA) concentrations after an overnight fast ...
Figure 7.9 The pattern of non-esterified fatty acid (NEFA) metabolism after an overnight f...
Figure 7.10 The milky appearance of blood plasma (right) after a fatty meal, compared with ...
Figure 7.11 Triacylglycerol concentrations in plasma after a meal. The figure shows concent...
Figure 7.12 The pattern of plasma triacylglycerol metabolism after a breakfast containing b...
Figure 7.13 Overview of protein and amino acid turnover in the body. We eat (very approxima...
Figure 7.14 The typical pattern of amino acid metabolism in different tissues. The diagram ...
Figure 7.15 The reactions that synthesise (glutamine synthetase) and break down (glutaminas...
Figure 7.16 Major amino acids interconversions in muscle. (Adipose tissue and brain may be ...
Figure 7.17 Major pathways for amino acid flow between tissues. The major sites of amino ac...
Figure 7.18 The intestinal-renal pathway. Enterocytes consume large amounts of glutamine (s...
Figure 7.19 Overall control of protein synthesis and breakdown in muscle (and other tissues...
Figure 7.3.1 Source: modified from Frayn, K. N. & Evans, R. D. (in press) Oxford Textbook of...
Figure 7.20 The glucose–alanine cycle operates in concert with the Cori (glucose–lactate) c...
Figure 7.21 Blood flow through adipose tissue and forearm muscle during a typical day with ...
Figure 7.22 Increasing fat storage with successive meals during a typical day with three me...

Chapter 8

Figure 8.1 Concentrations of ATP and of phosphocreatine (PCr) in Type II fibres in human m...
Figure 8.4.1
Figure 8.2 Coordinated regulation of glycogenolysis and contraction by Ca²⁺ ions in skelet...
Figure 8.5.1 Source: based on Newsholme, E. A., & Leech, A. R. (1983) Biochemistry for the M...
Figure 8.4 Relationship between initial glycogen concentration in the quadriceps muscle an...
Figure 8.5 Schematic drawing of the distribution of blood flow between various organs and ...
Figure 8.6 Plasma concentrations of cortisol (top panel) and growth hormone (bottom panel)...
Figure 8.7 Plasma glucose (top panel) and insulin (lower panel) concentrations during aero...
Figure 8.8 Coordination of metabolism by the nervous system during endurance exercise. Adr...
Figure 8.9 Glycogen concentrations in leg muscle after one-legged exercise (bicycling on a...
Figure 8.10 Plasma triacylglycerol (TAG) concentrations after a high-fat test meal on two o...
Figure 8.11 Offspring and maternal energy requirements in humans. Red circles represent foe...
Figure 8.12 Fuel disposition in the developing foetus. The foetus requires all three nutrit...

Chapter 9

Figure 9.1 The phases of starvation, assessed from the point of view of glucose metabolism...
Figure 9.2 Liver glycogen concentrations in normal human volunteers, after overnight fast,...
Figure 9.3 Rate of urinary nitrogen excretion in five obese subjects during starvation. So...
Figure 9.4 Serum concentrations of triiodothyronine (T₃) and reverse triiodothyronine (rev...
Figure 9.5 Concentrations of non-esterified fatty acids (NEFAs) and ketone bodies (the sum...
Figure 9.6 Major fuel flows in prolonged starvation. Protein (especially that in muscle) a...
Figure 9.7 Urinary nitrogen, phosphorus and sulphur excretion following major trauma. Sour...
Figure 9.8 Phases of metabolic change following acute injury, such as trauma. The ‘ebb’ ph...
Figure 9.9 Pattern of alteration of net nitrogen excretion and resting energy expenditure ...
Figure 9.10 Metabolic response to severe burn injury. Skin as injured tissue is both the or...
Figure 9.11 Interconnection of hormonal (both endocrine and cytokine) changes with immune s...
Figure 9.12 Changes associated with severe injury-sepsis and critical illness. The vertical...
Figure 9.13 The Warburg effect. Normal cells, when provided with adequate oxygen, mostly ox...
Figure 9.14 Altered metabolic pathways in cancer cells. Metabolism in tumour cells is direc...
Figure 9.15 Cancer cachexia. Characteristic loss of muscle tissue mass, with weakness, but ...
Figure 9.16 Effects of cancer growth on host metabolism and the aetiology of cancer cachexi...

Chapter 10

Figure 10.1 A typical lipoprotein particle.
Figure 10.2 The exogenous pathway of lipoprotein metabolism. Apo, apolipoprotein; FA, fatty...
Figure 10.3 The endogenous pathway of lipoprotein metabolism. Particles may undergo several...
Figure 10.3.1
Figure 10.4 HDL metabolism. Pre-β HDL is apolipoprotein AI (APOAI) associated with some pho...
Figure 10.5 Forward and reverse cholesterol transport. Cholesterol is secreted by the liver...
Figure 10.6 Relationship between risk of death from cardiovascular disease (coronary heart ...
Figure 10.7 Lowering of cardiovascular disease with reduction in serum cholesterol. The dat...
Figure 10.6-1 CETP, cholesteryl ester transfer protein (Section 10.2.3.2); TAG, triacylglycer...
Figure 10.8 Impaired postprandial triacylglycerol metabolism in patients with coronary hear...

Chapter 11

Figure 11.1.1 Summary of central pathways regulating appetite.
Figure 11.1 Relationship between serum leptin concentration and percentage body fat in 179 ...
Figure 11.2 Growth of a child with leptin deficiency due to a mutation in the leptin gene. ...
Figure 11.3 Antoine Lavoisier measuring the O₂ consumption of his assistant, Séguin. The pi...
Figure 11.3.1 Data for the example are reproduced from Garrow, J. S. (1988) Obesity and Relat...
Figure 11.4 Components of energy expenditure. A typical 24-hour energy expenditure of 10 00...
Figure 11.5 Relationship between body fat content and body weight in a series of 104 women....
Figure 11.6 Relationship between metabolic rate and fat-free mass (FFM; a measure of lean b...
Figure 11.7 Insulin resistance in obese men. Plasma glucose and insulin concentrations are ...

Chapter 12

Figure 12.1 A sufferer from Type 1 diabetes mellitus in the early days of insulin therapy, ...
Figure 12.2 Typical plasma glucose and insulin responses to a carbohydrate load in Type 2 d...
Figure 12.1.1 Redrawn from Felber, J. -P., Acheson, K. J., & Tappy, L. (1993) From Obesity to...
Figure 12.3 The metabolic pattern in untreated Type 1 diabetes. Pathways accelerated by ins...
Figure 12.4 Twenty-four-hour profiles of plasma glucose concentration in non-diabetic subje...
Figure 12.5 Twenty-four-hour profiles of plasma non-esterified fatty acid (NEFA) concentrat...
Figure 12.6 Plasma insulin concentrations in non-diabetic subjects and people with Type 1 d...
Figure 12.7 Non-enzymatic glycation of proteins. A sugar molecule in its straight-chain, al...
Figure 12.8 The polyol pathway for production and further metabolism of sorbitol. The enzym...

Preface

The first edition of Metabolic Regulation: A Human Perspective appeared in 1996. (It was pink.) When the second edition was published (in green) in 2003, it seemed that a revolution was taking place in metabolism. Tissues that we always thought were ‘doing metabolism’ turned out to be secreting hormones, adipose tissue and leptin being the prime example. By 2010, when the third (blue) edition was published, there were yet more changes in our understanding of metabolism and its regulation. The regulation of gene expression by nutrients (including, for instance, the carbohydrate-response element binding protein) was much better understood than previously. The techniques of genetic manipulation had also increased our understanding of metabolic pathways. In 1996, nobody could have guessed that a mouse without the adipose tissue enzyme hormone-sensitive lipase would be viable, let alone relatively normal: that finding led to the discovery of another enzyme of fat mobilisation, adipose triglyceride lipase. Similar studies made us revise our ideas about other ‘well-established’ enzymes such as phosphoenolpyruvate carboxykinase. Now, in 2018, we see more radical developments in the field. We always thought that hormones were hormones and metabolites were metabolites – now we know that the distinction is far from clear, with many compounds we regard as metabolites signalling through receptors as do ‘true hormones,’ thereby modulating metabolism. (We note in passing that the late Derek Williamson – colleague to both of us, and mentor to one [RDE], would not have been surprised: he had long predicted that the ketone bodies had a signalling role.)

We have always recognised that this textbook needed to be regarded as a complement to a more conventional biochemistry textbook, which would give details of pathways rather than just notes on their regulation. We have both taught metabolism to biochemistry and medical students in Oxford, and for this edition decided to combine our areas of expertise and to add material to the book that would enable it to be used more independently. Thus, in Chapter 1 of this new edition, we have provided overviews of metabolic pathways that will then be described in more detail in subsequent chapters. A particular emphasis of the later chapters, as in previous editions, is the tissue-specificity of these metabolic pathways. We are aware that this textbook is used by medical and nursing students and that has prompted us to include more material relevant to metabolism in clinical situations such as cancer, sepsis, and trauma. We hope this material will be of interest to all students, including those of nutrition and sports science, as it illustrates how metabolism may be perturbed. The small revision to the title of the book reflects these changes.

We thank Michael Goran, Fredrik Karpe, Denise Robertson and Garry Tan, who have helped us by reading, and commenting on, sections of the book. Any errors remaining are our responsibility. We are enormously grateful to Anne Clark, Mike Symonds and Roy Taylor for providing pictures and data. We give special thanks to Professor Rui Fontes of the University of Porto who translated edition 3 into Portuguese, and in so doing pointed out many errors, most of which had persisted through all the editions. Jenny Seward and James Watson, and their editorial team at Wiley, have been very helpful to us as we prepared this edition. Finally, we thank Theresa and Helen for putting up with us during the hours we spent at the computer producing this new edition.

Abbreviations

Some abbreviations used only within a figure, table or box, and defined there, are not included here. Some abbreviations are given in the text not because the terms are used frequently, but because the substance in question is often better known by its abbreviation. In such cases, if the abbreviation only occurs in one limited section, it will not be listed here.

ABC (G5, G8, etc.)	ATP-binding cassette-containing protein-G5, G8 etc.
ACAT	acyl-Coenzyme A: cholesterol acyltransferase
ACC	acetyl-CoA carboxylase
ACCORD	Action to Control Cardiovascular Risk in Diabetes
ACE	angiotensin-converting enzyme
ACS	acyl-CoA synthase
ACSL	long-chain acyl-CoA synthase
ACTH	adrenocorticotrophic hormone (corticotrophin)
ADH	antidiuretic hormone
ADP	adenosine 5′-diphosphate
AEE	activity energy expenditure
AGE	advanced glycation end-product
AgRP	Agouti-related protein
AIDS	Acquired ImmunoDeficiency Syndrome
ALT	alanine aminotransferase
AMP	adenosine 5′-monophosphate
AMPK	AMP-activated protein kinase
ANP	atrial natriuretic peptide
APOA, B, C, E, etc.	apolipoprotein A,B,C,E, etc.
ARB	angiotensin receptor blocker
AST	aspartate aminotransferase
ATGL	adipose triacylglycerol (or triglyceride) lipase
ATP	adenosine 5′-trisphosphate
BAT	brown adipose tissue
BCAA	branched chain amino acid
BCAT	branched chain amino acid aminotransferase
BCKD(C)	branched chain 2-oxoacid (α-ketoacid) dehydrogenase (complex)
BMCP1	brain mitochondria carrier protein 1
BMI	body mass index
BMR	basal metabolic rate
BNP	brain natriuretic peptide
cAMP	cyclic adenosine 3′, 5′-monophosphate (cyclic AMP)
CARS	compensatory anti-inflammatory response syndrome
CAT-1, 2	carnitine-acyl transferase-1, 2
CCK	cholecystokinin
CETP	cholesteryl ester transfer protein
cGMP	cyclic guanosine 3′, 5′-monophosphate (cyclic GMP)
CHD	coronary heart disease
ChRE	carbohydrate response element
ChREBP	carbohydrate response element binding protein
CIM	critical illness myopathy
CIP	critical illness polyneuropathy
CNP	C-type natriuretic peptide
CNS	central nervous system
CoA	coenzyme A
CoASH	coenzyme A reduced form
CoQ10	ubiquinone
CPT-1, 2	carnitine-palmitoyl transferase-1, 2
CSII	continuous subcutaneous insulin infusion
DHA	docosahexaenoic acid (22 : 6 n-3)
D-2HG	D-2-hydroxyglutarate
DIT	diet-induced thermogenesis
DPP	Diabetes Prevention Program
EDRF	endothelial-derived relaxing factor
EE	energy expenditure
eIF	eukaryotic initiation factor
eNOS	endothelial NO synthase
ER	endoplasmic reticulum
ERK	extracellular signal-regulated kinase
FABP(_pm)	fatty acid binding protein (plasma membrane isoform)
FAD	flavin adenine dinucleotide (oxidised form)
FADH₂	flavin adenine dinucleotide (reduced form)
FAT	fatty acid translocase
FATP	fatty acid transport protein
FFM	fat-free mass
FGF	fibroblast growth factor
FH	familial hypercholesterolaemia
FIL	feedback inhibitor of lactation
FoxO	Forkhead box ‘Other’
FQ	food quotient
FSH	follicle-stimulating hormone
FXR	farnesoid X-receptor
G	Gibbs ‘free’ energy
G6-P	glucose 6-phosphate
GDP	guanosine 5′-diphosphate
GH	growth hormone
GHSR	growth hormone secretagogue receptor
GIP	gastric inhibitory polypeptide, also known as glucose-dependent insulinotrophic polypeptide
GK	glucokinase
GLP (1 and 2)	glucagon-like peptide-1 and -2
GLUT	glucose transporter
GOAT	ghrelin-O-acyltransferase
GPAT	glycerol phosphate-acyl transferase
GPCR	G protein-coupled receptor
GPIHBP1	glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
GR	glucocorticoid receptor
GSK	glycogen synthase kinase
GTP	guanosine 5′-trisphosphate
HDAC	histone deacetylation/deacetylase
HDL	high density lipoprotein
HIF-1	hypoxia-inducible factor-1
HIV	Human Immunodeficiency Virus
HK	hexokinase
HMG-CoA	3-hydroxy-3-methylglutaryl-CoA
hPL	human placental lactogen
HSL	hormone-sensitive lipase
5-HT	5-hydroxytryptamine
IDDM	insulin-dependent diabetes mellitus
IGF	insulin-like growth factor
IL	interleukin
IMM	inner mitochondrial membrane
JAK	originally Just Another Kinase; redesignated JAnus Kinase
K_a	dissociation constant for an acid
K_m	Michaelis constant
LADA	latent autoimmune diabetes in adults
LCAD	long-chain acyl CoA dehydrogenase
LCAT	lecithin-cholesterol acyltransferase
LDL	low-density lipoprotein
LH	luteinising hormone
LPL	lipoprotein lipase
LXR	liver X-receptor
MAPK	mitogen-activated protein kinase
MET	(unit of work): 1 MET = resting metabolic rate
MI	myocardial infarction
MODS	multiple organ dysfunction syndrome
MODY	maturity-onset diabetes of the young
M_r	relative molecular mass
mRNA	messenger-RNA
MSH	melanocyte-stimulating hormone
mTOR	mammalian (or mechanistic) Target Of Rapamycin
NAD⁺, NADH	nicotinamide adenine dinucleotide (+, oxidised form; H, reduced form)
NADP⁺, NADPH	nicotinamide adenine dinucleotide phosphate (+, oxidised form; H, reduced form)
NAFLD	non-alcoholic fatty liver disease
Nam	nicotinamide
Nampt	nicotinamide phosphoribosyl transferase
NEAT	non-exercise activity thermogenesis
NEFA	non-esterified fatty acid
NHS DPP	NHS Diabetes Prevention Programme
NIDDM	non-insulin-dependent diabetes mellitus
NPC1L1	Niemann-Pick C1-like protein 1
NPR-A	natriuretic peptide-A receptor
NPY	neuropeptide Y
OMM	outer mitochondrial membrane
PAMPs	pathogen-associated molecular patterns
PCSK9	proprotein convertase subtilisin/kexin type 9
PDC	pyruvate dehydrogenase complex
PDH	pyruvate dehydrogenase
PDX1	pancreatic and duodenal homeobox 1
PET	positron emission tomography
PFK	phosphofructokinase
PGC	PPAR-γ co-activator
Pi, PPi	inorganic phosphate, pyrophosphate
PKA	protein kinase-A (cAMP-dependent protein kinase)
PKC	protein kinase-C
PKG	protein kinase-G (cGMP-dependent protein kinase)
POMC	pro-opiomelanocortin
PPAR	peroxisome proliferator-activated receptor
PPI	proton pump inhibitor
PTHrP	parathyroid hormone-related protein
RAAS	renin-angiotensin-aldosterone system
RAGE	receptor for advanced glycation end-products
RAS	renin-angiotensin system
REE	resting energy expenditure
RER	respiratory exchange ratio
ROS	reactive oxygen species
RQ	respiratory quotient
RXR	retinoid X receptor
SCN	suprachiasmatic nucleus
SGLT	sodium-glucose cotransporter
SIRS	systemic inflammatory response syndrome
SNP	single-nucleotide polymorphism
SOS	Swedish Obesity Study
SR	scavenger receptor
SREBP (-1c, -2)	sterol regulatory element binding protein (1c, 2)
STAT	Signal Transducer and Activator of Transcription
T₃	tri-iodothyronine
T₄	thyroxine
TAG or TG	triacylglycerol
TCA (cycle)	tricarboxylic acid (cycle)
TEE	total energy expenditure
TICE	trans-intestinal cholesterol efflux
TNFα	tumour necrosis factor-α
TNFR1, TNFRSF1A	TNF receptors
TR	thyroid hormone receptor
TSH	thyroid stimulating hormone
TTO (loop)	transcription translation oscillating loop
TZD	thiazolidinedione
UCP1,2,3	uncoupling protein 1, 2, 3
UDP-GlcNAc	uridine diphosphate N-acetylglucosamine
UKPDS	United Kingdom Prospective Diabetes Study
USF-1	upstream stimulatory factor-1
VCO₂	rate of CO₂ production
VLDL	very-low-density lipoprotein
V_max	maximal velocity of a reaction
VO₂ (max)	(maximal) rate of O₂ consumption