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Palmitoleic Acid and Insulin Resistance

What is insulin resistance

Insulin resistance

Glucose (energy) excess

The well-fed state - channeling all that energy into storage fat212 ([p 28-29])

  • In the well-fed state, increased levels of ATP and NADH --- markers of ‘cellular affluence’, inhibit the intermediate metabolism beyond citrate.
  • Levels of citrate and ATP thus increase.
  • Citrate along with the increased levels of ATP inhibit Phosphofructokinase-1 --- this inhibits the glycolysis pathway causing glucose to be shunted through the Pentose Phosphate Pathway [PPP] also known as the hexose monophosphate shunt
  • The pentose phosphate pathway is important for the production of NADPH used as a reducing agent in anabolic reactions and is essential for fatty acid synthesis.
  • Increasing amounts of Citrate cross the mitochrondrial membrane into the cystosol where it is split by citrate lyase to oxaloacetate + acetyl CoA
  • Citrate activates Acetyl CoA carboxylase, a regulatory enzyme controlling fatty acid synthesis in the liver and adipose tissue. Biotin is an essential cofactor for acetyl CoA carboxylase.
  • Glycerol 3-phosphate provides the backbone for the esterification process with palmitate

Summary of what happens to palmitic acid after it is formed from excess carbohydrate

  • A summary of the fate of palmitic acid follows

  • The liver, adipose (fat) tissue and lactating breast are the main tissues involved in triacylglycerol (triglyceride) production212.
  • When the body has more than enough energy supplies, the excess carbohydrate will be shunted off to create palmitic acid (a saturated acid) and this is then packaged into a triglyceride (tripalmitin)212 ie three palmitic fatty acids attached to a glycerol backbone to form the triglyceride.
  • The tripalmitin triglyceride can then be transported by VLDL to other tissues for storage, energy or other metabolic processes.
  • So it is interesting that an excess of carbohydrate intake will lead to an excess of a saturated fatty acid (palmitic acid) being formed.
  • Palmitoleate (a monounsaturated fat), can be formed from palmitic acid and this particular fatty acid acts as a lipokine (a fat hormone) to increase insulin sensitivity in muscle and liver.
  • Palmitoleate also decreases hepatosteatosis or fatty liver by decreasing the activity of a lipogenic enzyme in contrast to palmitate which increases fat storage in the liver.
  • Palmitic acid is also the starting point for elongation and desaturation processes that produce linoleic acid (linoleate) and the precursors to eicosanoid production.

Palmitoleate an omega-7 monounsaturated fatty acid is an important lipokine (lipid hormone) that can have a profound impact on insulin sensitivity in liver and muscle

  • Palmitoleate is a monounsaturated fat with a 16 carbon chain and a double bond between carbons 7 and 8 (POA, 16:1w7)198.

  • FABP 4 and 5 are the predominant fatty acid chaperones in adipose tissue
  • They guide the metabolism of the fatty acids
  • With a high fat diet, the FAB4/5 chaperones decrease de novo synthesis of fatty acids and hence decrease palmitoleate production
  • With lower fat diets, there is increased de novo synthesis of palmitoleate
  • Palmitoleate is then split from the triglyceride it is bound to by Hormone Sensitive Lipase (HSL) and moves to liver and muscle as a free fatty acid to work as a hormone (lipokine)

Increased insulin sensitivity in muscle and liver

  • In these tissues it works as a lipokine (a lipid hormone), to improve insulin sensitivity in liver and muscle, and in liver, to decrease hepatic fat stores (decrease hepatosteatosis or fatty liver)
  • High levels of Fatty ACYL-CoA derived from palmitic acid can be converted to ceramide217.
  • Palmitate can stimulate hepatic fat accumulation whereas palmitoleate can suppress the enzymes that cause this and antagonize the effects of palmitate216.

Natural sources of palmitoleic acid

Food Comment
Macadamia Nuts/Oil
  • Macadamia oil is 80% monounsaturated fat

  • Of this, 20% is made up of palmitoleic acid219 and 60% Oleic Acid.
Sea Buckthorn 
  • The oil of the sea-buckthorn is a rich source of this monounsaturated fat - palmitoleic acid (not to be confused with palmitic acid which is a saturated fat)

  • About 40% of the oil in sea-buckthorn is palmitoleic acid218.

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