Lipids

Lipids

1. Fats being hydrophobic in nature, they are insoluble in water and, therefore, cannot be transported in the blood plasma per se.

   • To allow these lipids to be transported through the bloodstream to various peripheral tissues, they must be made soluble by binding them to proteins. These proteins involved in lipid transport are known as apolipoproteins, and the protein-lipid particle is known as a lipoprotein.
     • Lipoproteins
       • Lipoproteins are the main transport mechanism for transporting lipids from the digestive tract to various parts of the body.
         • Lipoproteins depending on the specific apoproteins they contain and their size are:
           • Chylomicrons (CM)
           • Very low-density lipoprotein (VLDL)
           • Low-density lipoprotein (LDL)
           • High-density lipoprotein (HDL)
       • Lipoprotein metabolism
         • Exogenous route
           • Dietary fats are broken down by the action of pancreatic lipase and bile juices, to form micelles and small fat particles that are taken up by the intestinal epithelium.
             • After this uptake by enterocytes, they are packaged in conjunction with apolipoproteins, to form CM.
         • Endogenous route
           • This involves the synthesis, transport, and utilization of VLDL, IDL, LDL, and HDL.
       • Reverse cholesterol transport
         • While LDL is the main lipoprotein involved in the transport of cholesterol from the liver to peripheral tissues, HDL is responsible for the reverse process.
       • Lipoproteins and cancer
         • Rapidly dividing cancer cells require cholesterol as an essential component. LDL levels have been found to increase in various cancers.
           • In contrast, HDL levels have been found to have a negative correlation with the prevalence of most cancers.
       • ALZHEIMER disease
         • It is characterized by the deposit of amyloid beta (A β) in the brain, it can be affected by the association or not of A β in the brain with lipidated apolipoproteins E and J.
       • Lipoproteins and lungs
         • ApoA-1 and HDL have a protective role in normal lung health, and also in a number of diseases such as acute lung injury, COPD, pulmonary hypertension, and viral pneumonia.
       • Lipoproteins and immunity
         • Lipoproteins have been found to play a role in fighting certain viral and bacterial pathogens. The best studied example in this regard is the role of HDL in conferring immunity against Trypanosoma brucei in humans.
           • Viral infections
             • HDL particles have been found to have non-specific, broad-based antiviral activity against a broad spectrum of enveloped and non-enveloped DNA and RNA viruses.
           • Bacterial infections
             • Several classes of lipoproteins have the ability to neutralize lipopolysaccharides from gram negative bacteria.
               • Experimental infusion of synthetic HDL particles has been shown to have a protective role against gram-negative bacteremia and endotoxic shock.

2. Types of serum lipids

   • Triglycerides
   • Cholesterol
   • Fatty acids

3. Lipoprotein lipase

   • LPL is an extracellular enzyme that is essential in the metabolism of lipoproteins, it is a glycoprotein that is synthesized and secreted in various tissues (eg, adipose tissue, skeletal muscle, heart muscle, and macrophages)
     • LPL plays a key metabolic role by providing substrates for lipogenesis and lipid storage, and by supplying immediate energy for different tissues.
       • It has a relevance in chronic degenerative diseases such as dyslipidemia, obesity, type 2 diabetes mellitus and Alzheimer's disease, and in other contexts of altered lipid metabolism such as severe hypertriglyceridaemia and (potentially) associated acute pancreatitis, as well as nonalcoholic fatty liver disease.
         • Factors regulating LPL activity
           • LPL activity is finely regulated by a multitude of factors at the transcriptional, translational, and post-translational levels.
         • Alterations in LPL activity
           • Metabolic disorders are obesity, diabetes mellitus, dyslipidemia, metabolic syndrome, and osteoporosis.
   • Drugs and phytochemicals that affect LPL activity
     • Fibrates are one of the oldest lipid-lowering drugs.
     • Many plants rich in these phytochemicals, polyphenols, have now been tested for their effects on LPL activity.
     • Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, and acipimox) activate LPL, mainly reducing TG levels. Some statins, such as pitavastatin, simvastatin, and atorvastatin, also increase the expression and activity of LPL.