Blood-borne signals and eating

Question 1

Introduce how blood-borne signals affect eating

Answer 1

• Eating is one of the fundamental behaviours for survival.
• Yet, the systems responsible for determining when to east exist across a complex array of neural ciruitry and blood-borne signalling.
• This essay discusses the biological components of appetitite, with focus on hormonal signals, and evidence of their role in appetite control.

Question 2

What are the origins of our understanding of appetite?

Answer 2

• Nowadays we know a vast physiological system underlies the control of appetite.
• The roots of understanding began with Dr Friedman’s (1994) research on mice with defective ob genes displaying profound obesity and feeding behaviours.
• In 1995, Dr Friedman purified the ob gene product known as leptin, which provided a breakthrough in understanding. This important hormone will be discussed further on.

Question 3

Outline the neural circuitry involved in appetite control

Answer 3

• The neural circuitry responsible for changing appetite and food-seeking behaviours is located in the arcuate nucleus (first-order) and hypothalamus (second-order).
• The arcuate nucleus contains two sets of neurones: AGRP/NPY and POMC/CART.
• The former projects to the lateral hypothalamus (hunger centre) to promote increased food intake (appetite signals) through secretion of orexigenic peptides AGRP/NPY.
• The latter projects to the ventromedial hypothalamus (satiety centre) to promote reduced food intake (satiety signals) through secretion of anorexigenic peptides CART and alpha-MSH (Carlson, 2010).
• These modify the levels of orexin and MCH ultimately responsible for promoting ingestive behaviour.
• NPY also affects to paraventricular nucleus (PVN) to modify metabolic rate (Carlson, 2010).

Question 4

Discuss the role of hormones and the arcuate nucleus

Answer 4

• Hormones, such as leptin, serve as the input signals to the arcuate nucleus.
• There are a number of different appetite-related hormones produced from the digestive system and nutrient reservoirs (Carlson, 2010).
• Simply, hormones provide information of the body state to their brain.
• Four hormones are involved in regulating appetite: leptin, insulin, ghrelin, and peptide YY (PYY).

Question 5

Discuss the role of leptin in appetite and its evidence

Answer 5

• Leptin is continuously secreted by well-nourished adipocytes to act as a long-term anti-obesity satiety signal (Carlson, 2010).
• Conversly, falls in leptin levels indicate lipoprivation and act as appetite signals.
• Ob mice models administered with exogenous leptin showed significant increases in BMR, temperature, and satiety (Carlson, 2010).
• Leptin binds to receptors in the arcuate neucleus to inhibit AGRP/NPY neurones and stimulate POMC/CART neurones. This leads to reduction in orexin and MCH secretions from the lateral hypothalamus, decreasing food intake (Carlson, 2010).

Question 6

What is the relationship between leptin and obesity?

Answer 6

• Unfortunately, leptin administration is ineffective in combating the majority of obesity.
• This is because 90% of obese patients display leptin resistance rather than deficiency (Garrett, 2015).

Question 7

Discuss the role of insulin in appetite control and its evidence

Answer 7

• Insulin is responsible for transporting glucose from the blood into cells.
• It is secreted by beta cells in the islet of Langerhands of the pancreas (Carlson, 2010).
• Low level basal secretion occurs throughout the day during the non-fed state (Bilous & Donnelly, 2014), causing glucoprivation.
• Following mealtime, there is rapid higher-level secretion stimulating glycogenesis (Carlson, 2010).
• At moderately-high levels, insulin crosses the blood-brain-barrier, acting as a satiety signal.
• Similar to leptin, insulin binds with receptors in the arcuate nucleus for long-term inhibition of AGRP/NYP neurones and stimulates POMC/CART neurones to decrease food intake (Carlson, 2010).

Question 8

Outline the liver’s involvement in appetite control

Answer 8

• The liver possesses receptors sensitive to glucoprivation and lipoprivation, transmitting this information to the brain via the vagus nerve to stimulate eating (Carlson, 2010).
• Once these states are reversed, the liver sends signals via the vagus nerve to maintain satiety (Carlson, 2010).

Question 9

Discuss the the role of PYY in appetite control and its evidence

Answer 9

• PYY is a short-term anticipatory satiety signal proportionally secreted from the intestines based on preceding calorie and nutritional intake (Carlson, 2010).
• In animals and humans, it significantly decreases calories consumption (objective), plus reducing human hungar scores on VAS (subjective) (Batterham et al., 2002, 2007)
• At the arcuate nucleus, PPY suppresses NPY/AGRP neurones and subsequent appetite (Carlson, 2010).

Question 10

Discuss the role of ghrelin in appetite control and its evidence

Answer 10

• Ghrelin is a potent stimulator of appetite, with intraventricular injections also eliciting vivid imagery of food (Schmid et al., 2005).
• Its secretion is controlled by receptors in the duodenum activating upon food leaving the stomach (Carlson, 2010).
• Conversly, reductions in ghrelin serve as satiety signals.
• It is suggested that obese patients have defective ghrelin systems unresponsive to feeding.
• Prader-Willi syndrome is a genetic disease partly characterised by obesity and food-related behavioural problems (Henderson, 2015).
• These patients demonstrate high ghrelin prior to obesity, implicating its role for increasing appetite and causing obesity.
• Ghrelin knock-out mice display normal food intake and body weight (Sun et al., 2004); additionally being protected from overeating and weight gain when fed high-fat diets (Zigman et al., 2005).
• At the arcuate nucleus, ghrelin stimulates AGRP/NPY neurones and inhibits POMC/CART neurones, increasing appetitie (Carlson, 2010).

Question 11

Conclude the control of appetite

Answer 11

• In conclusion, biological control of ingestive behaviour involves neural circuitry in the hypothalamus and arcuate nucleus, plus hormone signalling.
• The hypothalamus serves as a relay point projecting to various areas of the brain to initiate food-seeking behaviours.
• The arcuate nucleus contains two competing areas. NPY/AGRP neurones activate to secrete orexigenic peptides that stimulate orexin and MCH secretion which increase food intake.
• POMC/CART neurones activate to secrete anorexigenic pepties that inhibit orexin and MCH secretion.
• Four hormones are involved in ingestive behaviour. Leptin and insulin are long-term satiety signals, whilst PYY is short-term. These activate during fed-states, actuing at the arcuate nucleus to inhibit AGRP/NPY and stimulate POMC/CART.
• Ghrelin is a potent appetitive signal produced during non-fed states to stimulate AGRP/NPY and inhibit POMC/CART.
• The subsequent hypothalamic signals decide if orexin and MCH are secreted, and if food-seeking behaviours are initiated.