L22 Obesity and Metabolic Syndrome

Question 1

How is appetite controlled?

Answer 1

Nucleus of the solitary tract (in the medulla) collects central and peripheral messages, including from anorexigens. This then sends messages to the arcuate nucleus.

Within the arcuate nucleus there are lots of neurones with different characteristics. Some are activated in an anorexigenic state (suppress hunger) causing them to secrete a range of substances. Orexigenic neurones secrete substances and integrate signals to drive appetite. They signal to a range of other hypothalamic nuclei such as the ventromedial nuclei (the satiety centre) and the lateral hypothalamic area (hunger centre).

Question 2

What is ghrelin?

Answer 2

It is a GH releasing hormone. It is released from the stomach when it is empty. It travels to the hypothalamus where it is a powerful orexigenic (appetite inducing) agent. Also acts as a neuropeptide in the brain (secondary transmitter).

Question 3

What are the anorexigens?

Answer 3

• CCK
  
  • Insulin
  • GLP-1 (Glucagon like peptide 1)
  • Peptide YY (produces from the colon and provides the ileal break and also goes to the brain and suppresses appetite)
  • Oxyntomodulin
    Somatostatin

Question 4

What is the role of leptin and adipokines in the control fo hunger?

Answer 4

Adipocytes are endocrine organs secreting messages to the body telling us how much fat we have, there are a range of adipokines. Leptin is an important adipokine. Leptin is important in the control of obesity as it leads to weight loss. Others such as TNF-alpha and IL-6 are pro-inflammatory cytokines, and inhibit insulin and leptin.

Question 5

Where are appetite signals integrated?

Answer 5

Hypothalamic nuclei such as the ventromedial nuclei (the satiety centre) and the lateral hypothalamic area (hunger centre).

Question 6

What happens in extreme starvation?

Answer 6

• Wasting of muscle
• Muscle fatigue and reduced exercise capacity
• Diminished respiratory capacity
• Slowed heart rate, and decreased contractility - due to thyroid hormone changes and a loss of heart mass
• Loss of heat-generating capacity - drop of thyroid hormone and reduced metabolic activity
• Apathy - due to reduced foodstuff for the brain
Death from respiratory or cardiac failure, or infection - become immunosuppressed as cortisol and other corticosteroids are immunosuppressing you

Question 7

What are the physiology effect of bulimia?

Answer 7

• Teeth are eroded away from the back due to vomiting as the acid comes up and dissolves the back of the teeth
• The hard palette is eroded away also
• Eroded right down to the bone due to local trauma - fingernail pressing down to make a person sick
• Would expect to see metabolic alkalosis due to loss of acid.
• Would expect the individual to be self-administering laxatives which lead to a loss of bicarbonate as parts of diarrhoea
  Use of diuretic can lead to hypokalaemia

Question 8

How is BMI related to health?

Answer 8

High BMI greatly increases your risk for:

• Gallstones
• Type 2 diabetes (striking)
• Hypertension
• CVD

Question 9

What are the physiological consequences of obesity?

Answer 9

Musculoskeletal system
• osteoarthritis (degeneration of joint cartilage & bone); lower back pain - this is due to a larger load on the bones and back
Circulatory system
• Hypertension (→ coronary heart disease, stroke & renal failure); deep vein thrombosis; pulmonary embolism - the fat has a rich blood supply and so the heart must do twice the work. It must work harder leading to HTN. We get deep vein thrombosis as travelling through the fat makes it slower.
Metabolic and endocrine systems
• Type 2 diabetes is substantially raised (65-75%); Dyslipidaemia; Metabolic syndrome (high blood glucose, blood pressure, cholesterol)
Cancers - due to the low grade inflammatory response
• endometrial, breast and colon cancers.
Reproductive and urological problems
○ stress incontinence, menstrual abnormalities, polycystic ovarian syndrome; infertility.
○ erectile dysfunction.
○ Offspring
Respiratory problems
• sleep apnoea
Gastrointestinal and liver disease
• non-alcoholic fatty liver disease; gastro-oesophageal reflux; gall stones.
Psychological and social problems
Stress; low self-esteem; social disadvantage; depression; reduced libido.

Question 10

What is the metabolic syndrome?

Answer 10

By definition you need a combination (3 out of 5) of:
• Obesity (waist circumference)
• Type II diabetes mellitus
• Hypertension
• High plasma triglycerides with 
• low HDL cholesterol

A syndrome is a cluster of symptoms that seem to go together. They are linked as obesity causes insulin resistance and both lead to production of proinflammatory cytokines (adipokines) which seem to underlie the CVD.