Hormones & Obesity

Question 1

What is obesity?

Answer 1

-Body Mass Index (BMI) = Weight in kg / (height in m)2
=Moderate 30-35
=Severe 35-40
=Very severe >40
-DEXA, skin fold thickness, MRI, BodPod – Not practical for routine clinical practice/public health
-Accumulation of adipose tissue

Question 2

When does obesity occur?

Answer 2

-Chronic energy intake (food, absorption) > energy expenditure (exercise, thermogenesis, basal metabolic rate, non purposeful activity/ restlessness) which
exceeds the capacity to respond
-Excess of just 50 kcal per day amounts to 2.5 kg in a year (insidious and slow)
-Genes (heritability 40-70%) x environment

Question 3

What are the efferents controlling body weight via hypothalamus?

Answer 3

-Satiety (default is to eat, behavioural aspects)
-Pituitary
=thyroxine from thyroid, cortisol from adrenal cortex, sex steroids (reproductive cycling), growth hormone
-Autonomic NS
=insulin from pancreatic beta cell (parasympathetic), adrenaline from adrenal medulla (sympathetic)

Question 4

What are the targets of regulation of body weight?

Answer 4

-Adipocytes
=differentiation, lipogenesis vs lipolysis, thermogenesis
-Muscle and liver= catabolic vs anabolic, impacted by cortisol, thyroxine, growth hormone and insulin

Question 5

What are the afferent signals that stop eating?

Answer 5

• Insulin (leaky median eminence)
• Ghrelin, PYY, GLP1= gastric distention in small bowel allows release
• Leptin from fat tissue= TNFa
• Conscious control (mood, emotional state)

Question 6

Describe Leptin

Answer 6

• Regulatory hormone
• Inherited factors
• Concentration corresponds to amount of fat tissue

Question 7

Describe leptin treatment for obesity

Answer 7

-Ineffective when [leptin] is high
› Idiopathic obesity
-Effective when [leptin] is low
› Leptin deficiency (rare)
› Anorexia nervosa
› Lipodystrophy

Question 8

What are the actions of leptin?

Answer 8

• Satiety- turns everything else off when absent
• Hypothalamic-pituitary-gonadal axis (burns energy so turns off)
› Puberty
› Fertility
• Hypothalamic-pituitary-adrenal axis
• Hypothalamic-pituitary-thyroid axis
• Peripheral actions??
› Adipocytes, pancreatic islets, immune cells, …

Question 9

What are the causes of secondary obesity?

Answer 9

• Hypothyroidism
• Cushing’s syndrome - usually iatrogenic
• Hypothalamic disease
• Others
› Drugs (oestrogen, beta blockers, tricyclic antidepressants,
sodium valproate)
› Insulinoma, GH deficiency
› Genetic Disorders: e.g. Prader Willi syndrome, Bardet Biedl syndrome, leptin or leptin
receptor deficiency, melanocortin 4 receptor defect, POMC deficiency,

Question 10

How are endocrine disorders in obesity spotted in a history?

Answer 10

› Always obese/age of onset?
› Periods regular/ headache/ thirst, polyuria?
› Diet, eating pattern, alcohol, exercise?
› Drugs?
› Complications and effects on lifestyle

Question 11

How are endocrine disorders in obesity spotted on examination?

Answer 11

› Features of Cushing’s, hypothyroidism, hypothalamic
disease, syndromes
› BP

Question 12

How are endocrine disorders in obesity spotted on investigation?

Answer 12

› TFTs
› Blood glucose
› ?o/n dex suppression test

Question 13

Why is obesity bad for you/ the consequences?

Answer 13

• Breathlessness and sleep apnoea
• Social and psychological effects
• Heart attack (atherosclerosis)
• Hypertension
• Diabetes mellitus
• Cancer (breast, endometrium, ovary, colon, gallbladder)
• Gallstones
• NAFLD
• Infertility and hirsutism
• Arthritis
• Varicose veins
• Incontinence

Question 14

How does obesity link with Type 2 diabetes?

Answer 14

-Genetically susceptible and put on weight= resistance to insulin
=more needs to be made so strain
=tired and turn off 60-70% turn off/ die

Question 15

How is obesity linked to breast cancer?

Answer 15

-Fat tissue converts testosterone into oestrogen post menopause
=oestrogen affect on cancer risk

Question 16

Describe apple fat distribution

Answer 16

-Central
-Visceral
-Android
-High risk
=fatty acids straight into liver?

Question 17

Describe pear fat distribution

Answer 17

• Peripheral
• Subcutaneous
• Gynoid distribution
• Low risk

Question 18

How is visceral fat worse than normal fat?

Answer 18

-different
metabolism or
secretion
-Releases free fatty acid direct to
liver converted into lipoproteins

Question 19

Describe Lawrence Syndrome

Answer 19

-Lipoatrophic diabetes
=fat cannot be stored
=ingested sugar circulates in excess
=autoimmune attack of fat tissue

Question 20

What are the insulin resistance complications of Lawrence Syndrome?

Answer 20

• Acanthosis nigricans
• Hyperandrogenism
• Female subfertility
• Precocious puberty
• Diabetes mellitus
• Soft tissue overgrowth

Question 21

What are the lipotoxic complications of Lawrence Syndrome?

Answer 21

• Severe dyslipidaemia
  • NAFLD, cirrhosis, HCC
  • Premature atherosclerosis
  • Diabetes mellitus

Question 22

What happens when adipose tissue storage capacity is exceeded?

Answer 22

-Extra-adipose fat stores= liver, muscle, pancreas
-Inflammation of adipose tissue
=foie gras
=lipodystrophy
=fatty liver disease/ muscle fat/ insulin resistance

Question 23

What are adipokines?

Answer 23

• Secreted from adipocytes or macrophages in adipose tissue, messenger hormones
• Manipulations in mice demonstrate potent effects on insulin sensitivity in other tissues
• Correlated with insulin sensitivity in other tissues in humans
• Many candidates published – variable importance in subsequent
studies

Question 24

What are the endocrine consequences of obesity?

Answer 24

• Altered steroid metabolism in adipose tissue:
› Increased oestrone and oestradiol
› Hirsutism and infertility
› Hormone-sensitive cancers
› Increased reactivation of cortisol from cortisone
• Altered substrate flux and adipose inflammation
› Insulin resistance
› Hyperglycaemia
› Dyslipidaemia, Fatty Liver
› Subfertility
• Altered hypothalamic function
› Anovulatory menstrual cycles
› Subfertility

Question 25

What are the strategies for manipulating body weight?

Answer 25

• Targeting appetite control/ satiety centres in CNS
• Altering adipocyte metabolism= turning on fat burning by activating brown/beige fat
• Bariatric surgery
• Combination hormones (medically mimicking surgery)
• Gut microbiota
• Public health measures/ education/ lows/ town planning

Question 26

Describe hormone effects on fat distribution

Answer 26

-Gynoid/ pear-shaped
=oestrogen
-Generalised
=thyroxine deficiency
-Android/ apple-shaped
=androgen
=cortisol
=growth hormone deficiency