2.3 Endocrine and Nervous System Regulation of Metabolism and Appetite
Key Takeaways
Insulin from pancreatic beta cells promotes glucose uptake, glycogen, fat, and protein synthesis, while glucagon from alpha cells raises blood glucose through glycogenolysis and gluconeogenesis.
Epinephrine, cortisol, glucagon, and growth hormone are counter-regulatory hormones that raise blood glucose during fasting and stress.
Leptin from adipose tissue signals satiety and energy sufficiency to the hypothalamus, while ghrelin from the stomach stimulates hunger.
The parasympathetic nervous system, mainly through the vagus nerve, stimulates digestion; sympathetic activation during stress slows digestion.
The brain uses glucose as its main fuel, about 120 g/day in adults, but adapts to use ketone bodies for much of its energy during prolonged starvation.
Endocrine and nervous control explains how the body moves between the fed and fasting states, why stress causes hyperglycemia and muscle loss, and how hunger is regulated. These systems appear in questions on diabetes, thyroid disease, obesity, and critical illness.
Major Endocrine Glands and Hormones
| Gland | Hormone | Main metabolic action |
|---|---|---|
| Hypothalamus | Releasing hormones (TRH, CRH, GHRH) | Controls the anterior pituitary |
| Anterior pituitary | GH, TSH, ACTH, prolactin, FSH, LH | Growth, thyroid and adrenal control, milk production, reproduction |
| Posterior pituitary | Antidiuretic hormone (ADH, vasopressin), oxytocin | Water reabsorption by the kidney; milk let-down and uterine contraction |
| Thyroid | Thyroxine (T4), triiodothyronine (T3), calcitonin | T3 and T4 set the basal metabolic rate; calcitonin lowers blood calcium |
| Parathyroid | Parathyroid hormone (PTH) | Raises blood calcium through bone resorption, renal reabsorption, and vitamin D activation |
| Adrenal cortex | Cortisol, aldosterone | Cortisol raises glucose and breaks down protein; aldosterone retains sodium and excretes potassium |
| Adrenal medulla | Epinephrine, norepinephrine | Fight-or-flight: glycogenolysis, lipolysis, higher heart rate |
| Pancreatic islets | Insulin (beta cells), glucagon (alpha cells), somatostatin (delta cells) | Blood glucose regulation |
| Adipose tissue | Leptin, adiponectin | Satiety signaling; insulin sensitivity |
| Kidney | Erythropoietin, renin, calcitriol | Red cell production, blood pressure, calcium absorption |
| Stomach and intestine | Ghrelin, CCK, GLP-1, PYY | Hunger and satiety, insulin release |
The thyroid needs iodine to make T3 and T4, and selenium-containing deiodinases convert T4 to the active T3.
Fed and Fasting States
| Feature | Fed state (insulin dominant) | Fasting and stress (counter-regulatory hormones dominant) |
|---|---|---|
| Blood glucose | Taken up by muscle and adipose (GLUT4) | Maintained by glycogenolysis, then gluconeogenesis |
| Liver | Glycogen synthesis, fatty acid synthesis | Glycogen breakdown, gluconeogenesis, ketone production |
| Adipose | Fat storage | Lipolysis releases fatty acids and glycerol |
| Muscle | Protein synthesis, glycogen storage | Protein breakdown supplies amino acids for gluconeogenesis |
| Key hormones | Insulin | Glucagon, epinephrine, cortisol, growth hormone |
Liver glycogen lasts only about 24 hours of fasting. After that, glucose comes from gluconeogenesis using amino acids (mostly from muscle), lactate, and glycerol. In prolonged starvation, ketone bodies spare protein by supplying much of the brain's energy. In stress states such as sepsis, trauma, and burns, high cortisol, glucagon, and catecholamines cause hyperglycemia, insulin resistance, and rapid muscle breakdown that feeding alone cannot stop.
Hormonal Regulation of Calcium and Fluids
- Calcium: low blood calcium raises PTH, which releases calcium from bone, increases renal reabsorption, and stimulates renal activation of vitamin D. Calcitriol increases intestinal calcium absorption.
- Water: rising plasma osmolality triggers thirst and ADH release, so the kidneys retain water.
- Sodium and volume: low blood volume activates the renin-angiotensin-aldosterone system, and aldosterone retains sodium and water.
Appetite Regulation
The hypothalamus integrates signals from the gut, fat stores, and brain:
- Hunger signals: ghrelin (stomach), neuropeptide Y and agouti-related peptide (hypothalamic neurons).
- Satiety signals: leptin (adipose tissue), insulin, cholecystokinin, GLP-1, peptide YY, and stomach distension, acting partly through POMC neurons.
- Leptin resistance: most people with obesity have high leptin levels, but the brain responds poorly to it.
Why weight loss triggers hunger. When body fat falls during dieting, leptin drops and ghrelin rises, which increases appetite, while resting energy expenditure falls somewhat more than predicted from the lost tissue. These adaptations help explain weight regain and are why long-term behavior support and physical activity matter in weight management. GLP-1 receptor agonist drugs act on the same satiety pathways to reduce appetite.
The Nervous System and Nutrition
| Division | Role in digestion and metabolism |
|---|---|
| Central nervous system | The brain uses about 20% of resting energy; glucose is its main fuel |
| Parasympathetic ("rest and digest") | The vagus nerve increases saliva, gastric acid, motility, and pancreatic secretion |
| Sympathetic ("fight or flight") | Slows digestion, raises blood glucose and heart rate |
| Enteric nervous system | The gut's own nerve network coordinates peristalsis and secretion |
Nutrients needed for nerve function:
- Thiamin: glucose metabolism in nerve tissue; deficiency causes Wernicke encephalopathy and dry beriberi.
- Vitamin B12: myelin maintenance; deficiency causes subacute combined degeneration.
- Vitamin B6: synthesis of neurotransmitters such as serotonin, dopamine, and GABA.
- Precursors: tryptophan for serotonin, tyrosine for dopamine and norepinephrine, choline for acetylcholine.
- DHA (omega-3): brain and retina development.
- Iodine: fetal brain development; deficiency causes cretinism.
Endocrine Disorders with Nutritional Consequences
| Disorder | Hormonal problem | Nutrition implication |
|---|---|---|
| Diabetes mellitus | Insulin deficiency or resistance | Carbohydrate control, weight management |
| Hyperthyroidism | Excess T3 and T4 | Higher energy and protein needs; weight loss |
| Hypothyroidism | Low T3 and T4 | Lower energy needs; separate levothyroxine from calcium, iron, and fiber |
| Cushing's syndrome | Excess cortisol | Central obesity, hyperglycemia, muscle and bone loss |
| Addison's disease | Low cortisol and aldosterone | Sodium loss, hyponatremia, hypoglycemia; needs adequate salt and hormone replacement |
| SIADH | Excess ADH | Water retention and dilutional hyponatremia; fluid restriction |
| Diabetes insipidus | Lack of ADH or kidney response | Large volumes of dilute urine; replace fluids |
Twelve hours after his last meal, a healthy man's blood glucose remains normal. Which hormone mainly maintains it at this point, and how?
Insulin, by stimulating glycogen synthesis in muscle
Leptin, by reducing glucose use by the brain
Aldosterone, by increasing renal reabsorption of filtered glucose
Glucagon, by stimulating liver glycogenolysis and gluconeogenesis
Most people with obesity have high blood leptin levels yet continue to feel hungry and gain weight. What best explains this?
Leptin resistance, in which the hypothalamus responds poorly to leptin
Leptin directly stimulates the stomach to secrete more ghrelin
High leptin increases thyroid hormone and appetite
Leptin is produced only in lean people
A patient with Addison's disease has fatigue, low blood pressure, hyponatremia, and episodes of hypoglycemia. Which dietary advice fits this condition while hormone replacement is adjusted?
Strict sodium restriction to 1,500 mg/day
Fluid restriction to 1 L/day
Adequate sodium and regular meals, since cortisol and aldosterone are deficient
A high-protein, very-low-carbohydrate ketogenic diet to stabilize blood glucose
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