Metabolic syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]
Overview
Metabolic syndrome are characterized by a cluster of conditions that greatly increases the risk of a person to develop heart diseases, diabetes and stroke. By definition one is said to have a metabolic syndrome if they have 3 of the following 5 conditions: high blood pressure (>130/85), abnormal fasting blood glucose > 100 mg/dl, increased weight around the waist (women > 35 inches, male > 40 inches), triglycerides > 150 mg/dl and a low HDL (female < 50, male < 40).
Pathophysiology
- The cause of the metabolic syndrome is unknown.
- The pathophysiology is extremely complex and has only been partially elucidated.
- Most patients are older, obese, sedentary, and have a degree of insulin resistance.
Insulin Resistance
Insulin resistance is considered the most acceptable hypothesis to describe the pathophysiology of metabolic syndrome. Free fatty acids, released from the expanding adipose tissue in obese patients, are the major contributors for the development of insulin resistance. In the liver elevated levels of these free fatty acids lead to increased production of glucose, TGs, VLDLs and LDLs. Free fatty acids inhibit insulin-mediated glucose uptake in the muscles. Increased circulating glucose stimulates increased pancreatic insulin secretion resulting in hyperinsulinemia. Excessive free fatty acids down regulate signalling pathways and lead to insulin resistance.
- The most important factors in order are 1) aging, 2) genetics and 3) lifestyle (i.e., decreased physical activity and excess caloric intake).
- There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if it is a by-product of a more far-reaching metabolic derangement [1]
- Systemic inflammation: a number of inflammatory markers (including C-reactive protein) are often increased, as are fibrinogen, interleukin 6 (IL−6), Tumor necrosis factor-alpha (TNFα) and others.
- Some have pointed to oxidative stress due to a variety of causes including dietary fructose mediated increased uric acid levels.[2][3][4]
- Commonly, there is development of visceral fat followed by the adipocytes (fat cells) of the visceral fat increasing plasma levels of TNFα and altering levels of a number of other substances (e.g., adiponectin, resistin, PAI-1).
- TNFα has been shown to not only cause the production of inflammatory cytokines, but may also trigger cell signaling by interaction with a TNFα receptor that may lead to insulin resistance.
- An experiment with rats that were fed a diet one-third of which was sucrose has been proposed as a model for the development of the metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance [5]. The progression from visceral fat to increased TNFα to insulin resistance has some parallels to human development of metabolic syndrome.
Associated Disorders
- Polycystic ovarian syndrome
- Hemochromatosis (iron overload)
References
- ↑ Després JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E; et al. (2008). "Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk". Arterioscler Thromb Vasc Biol. 28 (6): 1039–49. doi:10.1161/ATVBAHA.107.159228. PMID 18356555.
- ↑ Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ (2006). "A causal role for uric acid in fructose-induced metabolic syndrome". Am J Phys Renal Phys. 290 (3): F625&ndash, F631. PMID 16234313.
- ↑ Hallfrisch J (1990). "Metabolic effects of dietary fructose". FASEB J. 4 (9): 2652&ndash, 2660. PMID 2189777.
- ↑ Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ (1989). "Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch". Am J Clin Nutr. 49 (5): 832&ndash, 839. PMID 2497634.
- ↑ Fukuchi S, Hamaguchi K, Seike M, Himeno K, Sakata T, Yoshimatsu H. (2004). "Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats". Exp Biol Med. 229 (6): 486&ndash, 493. PMID 15169967.