White Adipose

• Hypertrophic adipose expansion

  • Increased adipocyte size
  • Linked to harmful phenomena
  • increased fatty acids release, pro-inflammatory cytokine release, immune cell recruitment, hypoxia, fibrosis
  • impaired insulin sensitivity.
• Lean adipose organ harbors various anti-inflammatory immune cells.

  Eosinophils, M2-like macrophages, Th2 cells, iNKT cells, and Treg cells.

  Maintain insulin sensitivity and store extra energy in the form of TGs.
• In obese adipose organ, the numbers of pro inflammatory immune cells are greatly elevated. Neutrophils, M1-like macrophages, mast cells, Th1 cells, and CD8 T cells.

  Simultaneously reduced number of anti-inflammatory immune cells.

  Accelerate pro-inflammatory response and adipose dysfunction.
• Obesity is associated with a cluster of metabolic abnormalities that is referred to as the metabolic syndrome
• metabolic syndrome: Glucose intolerance, insulin resistance, hyperinsulinemia, dyslipidemia, and hypertension.
• Obesity is a risk factor for a number of chronic conditions: Type 2 diabetes, dyslipidemias, hypertension, heart disease, some cancers, gallstones, arthritis, gout, and sleep apnea
• Obesity is correlated with an increased risk of death
• how to restore healthy fat distribution:

  1. diet and exercise, results in less weight, less liver fat, lot less visceral fat, and less subc. fat
  2. TZD: increased subc. fat, decrease liver fat, decrease visceral fat, increase weight
• Thiazolidinediones (TZDs), synthetic ligands of PPARγ, for the treatment of diabetes
• Thiazolidinediones (TZDs), synthetic ligands of PPARγ, for the treatment of diabetes

  • Promote adipogenesis, glucose uptake and TG storage in fat.
  • Reduce both insulin resistance and inflammation.
  • Unwanted side effects: weight gain, peripheral edema, bone loss,and congestive heart failure
• Lipodystrophy: A group of heterogeneous disorders characterized by varying degrees of body fat loss (lipoatrophy) or redistribution.
• Generalized lipodystrophy causes ectopic fat distribution inblood, liver, heart, muscle, heart, etc
• Endocrine funciton fo the white adipose organ:

  • Peptide hormones (adipokines),bioactive lipids (lipokines) andmicroRNA molecules
  • Local (autocrine & paracrine)and systemic (endocrine) effects
  • Secreted by adipocytes,endothelial and immune cells
• Leptin action during positive energy balance

  • During positive energybalance, WAT secrete moreleptin
  • Leptin acts on neurons in thehypothalamus to suppressfood intake while increaseenergy expenditure, in orderto restore energyhomeostasis.
• Leptin action during positive energy balance

  A) energy intake

  B) energy expentiture

  C) inc. fat deposition

  D) inc. leptin secretion

  E) incr. plasma leptin concentration

  F) altered activity of integrating centers

  G) dec. energy intake

  H) inc. metabolic rate

  I) -

  
• Therapeutic applications of Leptin

  Can Leptin be used to treat obesity?

  • Congenital leptin deficiency is a rare disorder (only a few dozen casesreported).
  • Hyperleptinemia & leptin resistance observed in general obesity.
• Leptin action during negative energy balance(more important function of leptin)

  • During negative energybalance, WAT secrete less leptin
  • The reduction in leptin levels promotes food intake while decreases energy expenditure, in order to restore energy homeostasis.
• Leptin action during negative energy balance(more important function of leptin)

  • During negative energybalance, WAT secrete less leptin
  • The reduction in leptin levels promotes food intake while decreases energy expenditure, in order to restore energy homeostasis.
  • Drop in leptin levels protects from the risks (starvation & infertility) associated withbeing too thin.
• Leptin action during negative energy balance(more important function of leptin)

  A) energy intake

  B) energy expenditure

  C) decrease fat deposition

  D) decrease leptin secretion

  E) decrease plasma leptin concentration

  F) altered activity of integrating centers

  G) increasing energy intake

  H) decreasing metabolic rate

  I) +

  
• Therapeutic applications of Leptin

  Glucoregulatory actions of leptin

  • Effects of leptin on glycaemia can beseparated from its effects on bodyweight and food intake
  • Leptin was ineffective in improvinginsulin sensitivity and glycemic control inobese individuals with type 2 diabetes.
  • Leptin may have antidiabetic (type 1)actions.
  • Leptin therapy reverses insulinresistance and improves glycemic controlin patients with lipodystrophy