Human Body Temperature Regulation

Homeostasis

• Homeostasis is the body's ability to maintain relatively constant internal conditions within defined limits.
• Claude Bernard first described this concept in relation to internal bodily systems.
• Walter Cannon later coined the term "homeostasis" in 1929.
• Homeostasis involves optimal body temperature (for humans, 36°C to 38°C), optimal blood concentrations of various substances (sugars, proteins, sodium, potassium, etc.), and optimal blood pH.

Homeostasis and Behavior

• Many homeostatic systems are entirely physiological, but some also involve behavioral components.
• A key example is the maintenance of water and salt balance (drinking behavior).
• Physiological systems (like aldosterone production by the adrenal glands) are not always sufficient for balance.
• Behavioral compensatory mechanisms can be crucial in such cases, as seen in adrenalectomized rats.

Pica in Humans

• Pica is a disorder where individuals consume inedible/non-food items.
• It's named after the European magpie (Pica pica).
• Pica is commonly observed in young children, pregnant people, and those with certain mental health conditions.
• A link often exists between pica and nutritional deficiencies (e.g., calcium, iron, zinc).

Hormones and Homeostasis

• Many hormones involved in physiological homeostasis also mediate behaviors vital for homeostasis.

Archetypal Homeostat

• The archetypal homeostatic device is a thermostatically controlled heating and cooling system.
• Humans maintain a core body temperature of approximately 37°C
• Variations in temperature up to 35°C to 38°C are not life-threatening.

Poikilothermic Organisms (Lizards)

• Lizards, as poikilothermic animals, can regulate their body temperature through behavioral means.
• Experiments show that lizards adjust their set points in response to infections.

Set Point Concept

• The concept of a set point is valuable for systems requiring precise regulation.
• It's less useful for systems that can tolerate wider variations.

Fluid Balance

• Homeostatic mechanisms regulate water and sodium balance (intake and excretion).
• Water is essential for virtually all metabolic processes.
• Water loss through perspiration, respiration, urination, and defecation must be constantly replenished.
• If water use exceeds intake, the body conserves water.
• Behavioral compensation is necessary if physiological conservation is insufficient.

Sodium and Water Regulation

• The regulation of sodium and water is closely linked.
• Sodium is crucial in moving water between compartments (extracellular and intracellular).
• Cell membranes act as barriers between these compartments.
• Osmotic balance between compartments is critical for maintaining water balance.

Vasopressin and Kidneys

• Vasopressin conserves water in the kidneys.
• If excessive water is consumed, reduced plasma osmolality inhibits vasopressin release leading to increased urine production (diuresis).

Blood Plasma Volume

• A different regulatory system maintains blood plasma volume.
• Loss of fluid/electrolytes leads to hypovolemic thirst.
• Kidney function compromise can lead to fluid imbalances.

Endocrine Regulation of Fluid Balance and Thirst

• Vasopressin acts on the kidneys to retain water.
• Genetic mutations related to vasopressin production lead to diabetes insipidus.

Cerebral Osmoreceptors

• Cerebral osmoreceptors signaling the hypothalamus regulate vasopressin production based on dehydration levels.

Insulin and Blood Plasma Volume

• Stretch receptors in cardiac blood vessels regulate vasopressin and signal via the vagus nerve for thirst in response to blood plasma volume changes.
• Hypovolemia leads to angiotensin production and aldosterone release.
• Aldosterone promotes sodium retention and reduces urine production.

Sodium Balance

• Interstitial fluid sodium reservoirs buffer brain cells from sodium fluctuations.
• Insufficient sodium necessitates seeking and consuming it.

Energy Balance

• Animals must consume food for raw materials and energy.
• The balance between energy storage, expenditure, and intake varies across species.
• Mechanisms for stopping eating (satiety signaling) are often weaker than hunger signals.

Long-Term Energy Balance

• Homeostatic mechanisms control long-term body mass within a relatively fixed range over weeks, months, or years.

Food Consumption – Humans

• Human food intake relies on endogenous signaling, experiences, habits, mood, and availability.
• Anticipation of food can affect associated hormones.

Gut Hormones

• Several gut hormones function to increase fuel absorption, oxidation, thermogenesis, and body temperature.
• Gut hormone secretion is generally proportional to calorie consumption.

Metabolism During Well-Fed State

• Two phases of energy utilization/storage follow food consumption.
• Postprandial phase: metabolic fuels enter the bloodstream.
• Postabsorptive phase: excess energy is stored. -Two distinct phases of insulin release: Cephalic and Gastrointestinal.

Metabolism During Fasting State

• When energy intake is insufficient, energy must be obtained from storage.
• The brain needs a consistent energy supply.
• Pancreatic glucagon release prompts lipolysis and glycogenolysis.
• Gluconeogenesis occurs in the liver.
• SNS also stimulates fat breakdown.

Dysregulated Energy Metabolism

• Problems taking up energy into cells can arise from insulin issues.
• Diabetes mellitus type I (autoimmune destruction of pancreatic insulin-producing cells).
• Diabetes mellitus type II (tissue insensitivity to insulin).

Diabetes Symptoms

• Elevated appetite.
• High blood sugar (hyperglycemia).
• Increased thirst.
• Increased urination.

Measuring Fuel Oxidation

• Animals with diabetes mellitus are used to study fuel oxidation's role in food intake.
• Food intake is related to fuel availability, not just circulating levels.

Hyperinsulinemia

• Hyperinsulinemia is the condition where individuals produce too much insulin.
• It leads to increased glucose uptake, inhibited lipolysis, and low blood sugar.
• Obesity is a potential result.

Primary Sensory Signals

• Preparatory factors (prior to food intake) influence hormone production.
• A fixed meal schedule demonstrates significant anticipatory ghrelin release in humans and rats.

Control of Food Intake

• Humans eat based on internal and external cues.
• Factors include how much to consume, what kind of food to consume, when to start eating, and when to stop.
• Consumption of the wrong calorie-dense foods disrupts normal hormonal processes and may drive cravings, hunger, or over-consumption.
• Eating depends on intrinsic factors (e.g., stored energy, food composition, gut signals) and extrinsic factors (availability, culture, environment).

Hunger

• Hunger is the motivated seeking and consuming of food.
• It's a psychological state that's triggered by decreases in satiety.
• The body monitors long-term energy stores, intake, and utilization.

Peripheral Signals

• Food intake is regulated based on intracellular changes.
• A sensory system monitors metabolic fuel levels, oxidation, storage, and breakdown.
• This regulation controls food intake, energy expenditure, and body fat storage/breakdown.

Leptin

• Leptin is produced by fat cells (adipose tissue) and acts as a satiety hormone.
• Leptin levels are proportional to body fat.
• Leptin does not consistently prove effective for long-term weight loss.
• Leptin is too large to pass the blood-brain barrier directly, must be transported.
• Leptin's effects on the brain include inhibiting eating and influencing reproduction.

Insulin

• Insulin is another key adiposity signal.
• Hunger occurs when insulin levels drop.
• Insulin signals to the brain through the cerebrospinal fluid.
• Insulin receptors exist in the brain, especially in the hypothalamus (arcuate nuclei).

Gastrointestinal Tract Hormones

• Most GI tract hormones (e.g., pancreatic polypeptide, peptide YY, glucagon-like peptide 1) are involved in decreasing food intake.
• Ghrelin, produced in the GI tract, stimulates food intake and works oppositely to leptin.

Central Signals

• The arcuate nuclei, lateral hypothalamus, and paraventricular nucleus are main control points of food intake.
• The arcuate nuclei have opposing neural circuits controlled by peripheral hormone signals (related to food, fat stores, etc.).

Central Signals – Feeding Stimulatory Circuit

• Neurons in the feeding stimulatory circuit produce NPY and AgRP.
• NPY directly evokes feeding behavior.
• AgRP inhibits melanocortin receptors, hence affecting appetite.

Central Signals – Feeding Inhibitory Circuit

• CART and POMC are key signaling molecules in the feeding inhibitory circuit.
• Increased CART secretion decreases food intake.
• POMC produces a-MSH, inhibiting appetite.
• High levels of insulin and leptin drive POMC and CART activity, hence reducing food intake.

Hindbrain and Brainstem

• The hypothalamus is a major area, but other posterior brain areas can exert control over food intake independently.
• Studies using rats with isolated hypothalamus showed food intake responses to glucose and fatty acid metabolic blockage.

Protein Hormones

• Long delays between nutrients leaving the gut and use/storage could lead to other signaling mechanisms.
• Neural signals from stomach distension play a role.
• The rate of digestion is likely involved in signaling satiety.

Endocrine Signals That Stop Feeding

• Cholecystokinin (CCK) is a key hormone associated with satiety.
• CCK works by influencing the gut and the brain stem.

Other Signals

• Bombesin.
• Amylin, similar to insulin's regulating effects.
• Corticotropin-releasing hormone (CRH): rapidly decreases food intake. -The sympathetic nervous system connects adipose tissues and the brain. -Chronic stress affects the HPA axis leading to changes in food intake. -Other hormones, like GLP-1, adiponectin, and PYY, also likely affect feeding behavior.

Other Factors Influencing Food Intake

• Endorphins may influence food intake.
• Treatment with the opioid antagonist naloxone reduces food intake.
• Sugars and oils appear associated with endorphin release.
• Comfort food potentially also involves similar signaling.

Gonadal Steroid Hormones

• Gonadal steroids influence feeding behavior and subsequent body mass.
• Evidence shows appetite regulation links closely to reproductive behavior.
• Estrogen generally increases energy expenditure, while progesterone has a potentially opposite influence.
• Hormonal changes through the ovarian cycle influence eating and body mass in rats and primates.

Adipose Tissue Metabolism

• Adipose tissue has receptors for estrogens and progestins.
• Estradiol decreases lipoprotein lipase (LPL) activity.
• Progesterone increases LPL activity.

Androgens

• Sexual dimorphism (differences in size between sexes) appears to be affected by androgens peri-natally.
• Androgens also influence the degree of dimorphism throughout time.
• Castration in rats reduces food intake and limits weight gain, including muscle mass.