Hormones & Obesity Flashcards
What is obesity?
-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
When does obesity occur?
-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
What are the efferents controlling body weight via hypothalamus?
-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)
What are the targets of regulation of body weight?
-Adipocytes
=differentiation, lipogenesis vs lipolysis, thermogenesis
-Muscle and liver= catabolic vs anabolic, impacted by cortisol, thyroxine, growth hormone and insulin
What are the afferent signals that stop eating?
- Insulin (leaky median eminence)
- Ghrelin, PYY, GLP1= gastric distention in small bowel allows release
- Leptin from fat tissue= TNFa
- Conscious control (mood, emotional state)
Describe Leptin
- Regulatory hormone
- Inherited factors
- Concentration corresponds to amount of fat tissue
Describe leptin treatment for obesity
-Ineffective when [leptin] is high › Idiopathic obesity -Effective when [leptin] is low › Leptin deficiency (rare) › Anorexia nervosa › Lipodystrophy
What are the actions of leptin?
• 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, …
What are the causes of secondary obesity?
• 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,
How are endocrine disorders in obesity spotted in a history?
› Always obese/age of onset?
› Periods regular/ headache/ thirst, polyuria?
› Diet, eating pattern, alcohol, exercise?
› Drugs?
› Complications and effects on lifestyle
How are endocrine disorders in obesity spotted on examination?
› Features of Cushing’s, hypothyroidism, hypothalamic
disease, syndromes
› BP
How are endocrine disorders in obesity spotted on investigation?
› TFTs
› Blood glucose
› ?o/n dex suppression test
Why is obesity bad for you/ the consequences?
- 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
How does obesity link with Type 2 diabetes?
-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
How is obesity linked to breast cancer?
-Fat tissue converts testosterone into oestrogen post menopause
=oestrogen affect on cancer risk
Describe apple fat distribution
-Central
-Visceral
-Android
-High risk
=fatty acids straight into liver?
Describe pear fat distribution
- Peripheral
- Subcutaneous
- Gynoid distribution
- Low risk
How is visceral fat worse than normal fat?
-different metabolism or secretion -Releases free fatty acid direct to liver converted into lipoproteins
Describe Lawrence Syndrome
-Lipoatrophic diabetes
=fat cannot be stored
=ingested sugar circulates in excess
=autoimmune attack of fat tissue
What are the insulin resistance complications of Lawrence Syndrome?
- Acanthosis nigricans
- Hyperandrogenism
- Female subfertility
- Precocious puberty
- Diabetes mellitus
- Soft tissue overgrowth
What are the lipotoxic complications of Lawrence Syndrome?
- Severe dyslipidaemia
• NAFLD, cirrhosis, HCC
• Premature atherosclerosis
• Diabetes mellitus
What happens when adipose tissue storage capacity is exceeded?
-Extra-adipose fat stores= liver, muscle, pancreas
-Inflammation of adipose tissue
=foie gras
=lipodystrophy
=fatty liver disease/ muscle fat/ insulin resistance
What are adipokines?
• 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
What are the endocrine consequences of obesity?
• 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
What are the strategies for manipulating body weight?
- 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
Describe hormone effects on fat distribution
-Gynoid/ pear-shaped =oestrogen -Generalised =thyroxine deficiency -Android/ apple-shaped =androgen =cortisol =growth hormone deficiency
