Psyc*3410- Hunger, Satiety and the Brain

Early Studies of hunger and the brain

brainstem: decerebrated rats show fairly normal eating

Hypothalamus: old lesion and stimulation studies

1. Lateral hypothalamus (LH) as feeding centre

2. Ventromedial hypothalamus (VMH) as satiety centre

Hypothalamic Control of Feeding: Ventromedial Hypothalamus Lesions

Lesions to the VMH cause VMH syndrome

- hyperphagia (excessive eating)

- preference for palatable food (finicky)

- Dynamic phase: excessive eating -> very rapid weight gain

- Static phase: stabilized (but still high) eating -> new weight becomes stable

Hypothalamic Control of Feeding: Lateral Hypothalamus Lesions

Lesions to the LH cause LH syndrome

- aphagia (cessation of eating)

- adipsia (cessation of drinking)

However: lesions produce severe motor disturbances and general lack of responsiveness to sensory input

Updated Role of the Hypothalamus in hunger and eating

Lateral Hypothalamus

Paraventricular Hypothalamic Nucleus

Arcuate Hypothalamic Nucleus

What about the VMH?

Role of Hypothalamic Nuclei in Hunger and Eating

Role of Hypothalamic Nuclei in Hunger and Eating: Summary

Arcuate NPY neurons

- Neuropeptide Y (NPY): feeding enhancer

- Agouti-related peptide (AgRP): feeding enhancer

Arcuate POMC neurons

- Melancortins (agonist of MC4 receptor): feeding inhibitors

Lateral hypothalamus

- melanin-concentrating hormone (MCH): feeding enhancer

- Orexins (A and B)/hypocretins: feeding enhancers

Paraventricular hypothalamic nucleus

- feeding inhibitor and metabolism enhancer

Distinct roles in hypothalamic nuclei in the regulation of food intake, energy expenditure, and glucose and lipid metabolism in peripheral tissues by leptin

Control of Food intake by the hypothalamix leptin-melanocortin pathway

Role of Hypothalamic Nuclei in Hunger and Eating: What about the Ventromedial Hypothalamus

Most effects due to changes in metabolism (not feeding behaviour)

- insulin levels increase

- lipogenesis (formation of fat) increases

- lipolysis (breakdown of fat) decreases

- most energy stored as fat

- rats need to get more energy, therefore eat more

Other effects due to unwanted lesions

- paraventricular nucleus of the hypothalamus

- noradrenergic bundle

Role of leptin in hypothalamic regulation of hunger and eating

Secreted by adipose tissue

- long term satiety signal

- regulatin of body fat/composition

- inhibits NPY neurons

- stimulates POMC neurons

-Net effect = eat less food, burn more calories

Feeding inhibitors

Cholecystokinin (CCK)

Bomesin

Glucagon

Somatostatin

Leptin

Monoamines

Motilin

Melanocortins

- alpha-melanocyte-stimulating hormone

Immune-related peptides

Urocortin

Peptide YY

Feeding enhancers

Neuropeptide Y

Orexin-A

Ghrelin

Opiods

Galanin

Catecholamines

Effects of Food Restriction

Evidence suggesting enhancement of health and longevity in food restricted humans and animals

Humans: "The Okinawa Paradox", 20-38% food restriction

Mice: up to 65% less food than free-fed

Chronic caloric restriction and intermittent fasting

Hypotheses for the benefits of food restriction

1. Accumulation of by-products of energy consumption accelerates aging

2. Activation of conservation/survival mechanisms that protect cells from damage -> prolong cells' live -> slow organ aging

Things to consider regarding food restriction

- In mice, food restriction directly triggers activation of factors that regulate energy balance and promote longevity

- Life expectancy and longevity have declined in Okinawa since the1960s; younger Okinawans have higher average BMI, not enduring calorie restriction▪ However:

-People are not mice. -the actual probability for individuals 70 years old in 1975 of becoming centenarians in 2005 was 3 times higher, on average, in Okinawa ...than in Japan as a whole

-Historical disenfranchisement and post-WWII military occupation

-Diet quality - nutrient- and anti-oxidant-dense foods

- Strong social support

Regulation of Body Consumption: Energy Consumption

Not just what/how much we eat but also energy usage

Daily energy consumption:

- basal metabolic rate

- diet-induced thermogenesis/ thermal effects of food

- physical activity (exercise activity thermogenesis)

- non-exercise activity thermogenesis

Changes in the Efficiency of Energy Use

Decrease in body fat = more efficient fat usage

Increase in body fat= less effective fat usage

Adjustments in diet-induced thermogenesis:

- decrease in body fat= decrease in body temp

- increase in body fat= increase in body temp

- changes in the efficiency of energy use are why weight loss and weight gain programs are more effective in their initial phase

Changes in Body Composition and Energy Use

Body Composition Regulation: Setting-Points Theory

Not just fat regulation -> various factors

A loose concept of homeostasis

Long term changes in various factors -> body composition changes

Feedback mechanisms -> limit the impact of changes

(leaky barrel)