Obesity & Related DiseasesObesity is a disease that is a resultant of accumulation of excess body fat that brings the BMI to >25 in normal humans. BMI is used widely as an indication of presence of other health problems namely blood pressure health, cardiovascular, and liver problems. The usual causes of obesity will be omitted in this article, with elaboration more on two levels: Mitochondrial disorders, and subgroup Fatty acid disorder, more specifically (Carnitine Deficiency).
The symptoms of interest from obesity are decreased energy levels and excess body fat. Decreased energy levels are indicative of essentially mitochondrial defects, caused by either insulin resistance (IR) further upstream of the respiratory chain or inhibition/deficiency of transporters of the mitochondrion. Primary carnitine deficiency is due to a mutation in the SLC22A5 gene, where the body is unable to retain sufficient carnitine. Carnitine is an important amino acid-like substance in the body which is used to transport fatty acids to the mitochondrial matrix, thus facilitating fat oxidization. The mutation causes carnitine to be lost by urine, resulting in reduced carnitine levels in the tissue. There are different kinds of fat in the body where brown fat; which maintains body warmth and when stimulated, actually helps burning of calories and is the most beneficial. There is also white fat, which stores energy and produces regulatory hormones. Lastly, the most harmful is visceral fat, which is thought to play a increased role in insulin resistance and diabetes. Reduced carnitine levels makes the body unable to use fat as a source of energy. As fat is not used as a source of energy, there will be an accumulation of unhealthy fat in organs like the liver, heart and muscles causing complications like Non-alcoholic fatty liver disease (NAFLD). NAFLD is where there is an increase of lipids in hepatic cells. This will lead to increased insulin resistance (IR) in the liver, causing higher hepatic glucose output and resulting to type 2 diabetes. Peripheral IR will cause an increase in free fatty acids (FFAs) and resulting to triglyceride accumulation in the liver. Excess FFAs will prevent kinase activation, leading to stress response being activated. |
This stress response will cause the activation of a number of cytokine genes, producing an inflammatory response which would in turn result in insulin resistance. Hepatic IR will cause an increase expression of element-binding protein-1c (SREBP-1c) which will inhibit carnitine palmitoyl transferase-1 (CPT-1). Inhibition of CPT-1 will cause the body to be unable to utilize fat as source of energy by interfering with glyconeogenesis, glycolysis, and the Kreb's cycle in bodily metabolism. Ultimately leading to excess amounts of fat being stored but not utilized, leading to obesity.
Treatments for mitochondrial disorders include an increased protein diet and vitamin supplementation, as well as sufficient hydration. This is to optimize the energy required for normal cellular functions and health. For individuals who only suffer from carnitine deficiency, carnitine supplements would help optimize this. We have highlighted Olive Oil as a supplement for mitochondrial diseases. It contains chemical hydroxytyrosol which is beneficial due to its antioxidant effects that counter the mitochondrial stress caused by oxidation by providing component Coenzyme Q. It also provides an essential regulation of cholesterol levels which contribute to artherocelerosis and fatty acid buildup. Ideally, treatment for obesity is constant and well rounded exercise coupled with a holistic diet supplemented with sufficient vitamins and nourishment. Muscle ultimately oxidizes fat better and produces positive hormones that allow the mitcohondria to better cope with oxidative stress and the improves metabolism and circulation. Dealing with obesity and related problems is a long-term effort where prevention is ultimately better than cure. *Further detailed information is available in individual blog posts in our Relevant Articles Tab. For any queries or any information that you would like to see, please comment on our blog posts. Last Edited at 4.12pm 17th January 2013 by: Charles Yong Heng |