Fatty Muscle & Insulin Resistance

Fatty Muscle (Intramyocellular Lipid) and Insulin Resistance

Healthy people have very little fat in their muscles because the fat cells (adipocytes) are specialized to store fat. Any other organs, as well as skeletal muscles, are not meant to be caught clogged up with fat. Ectopic fat deposits, meaning fats displaced anywhere else than the adipocytes, lead to abnormalities and insulin resistance. [1]

Many studies have revealed the associations between insulin resistance and body fat distribution, particularly the fat distribution in skeletal muscle, as this tissue is responsible for the majority of whole-body insulin-stimulated glucose disposal. Skeletal muscle insulin resistance is central to type 2 diabetes. [2]

As Dr. Jason Fung states in his book “The Diabetes Code,” (which I highly recommend reading) states, “The accumulation of fat in the liver is the cause of insulin resistance in the liver. The accumulation of fat in the muscles is the cause of insulin resistance in the muscles. Hyperinsulinemia forces too much fat and glucose inside the skeletal muscle. […] Since the skeletal muscle is so large, they contribute significantly to overall insulin resistance in the body”..” [3]

Eating fructose, sugar, and refined carbohydrate multiple times a day results in hyperinsulinemia, which in turn forces the liver to generate new fat and store it in adipose tissue. As soon as the adipose tissue is challenged, the surplus fat is distributed throughout the body. The stored fat in muscles is called intramyocellular lipid, meaning the fat between muscle cells.

The Randel Cycle

In 1963, Lancet published a paper by Dr. Philip Randel et al, that explained the inhibition of glucose oxidation by fatty acids. Since then, the principle has been confirmed by many investigators. [4] Let’s take a very over-simplified look at this.

In the fasting state, almost all cells burn fat for fuel to spare glucose for some regions in the brain that exclusively use glucose for energy. The liver also produces and supplies 75% of the brain’s energy demand by ketone bodies, in order to conserve glucose. The opposite is also true, in the fed state, the body switches to burning glucose for fuel and banks up the fat for the times when we are not eating. This evolutionary mechanism extends the time we can survive without eating.

The reinforcing factor of fat accumulation in the muscles is, that the cells are not able to burn glucose and fat simultaneously. They burn only fat or glucose at any given time. [5] In other words, when the cell is full of glucose, the fat oxidative capacity is significantly reduced, which leads to further fat aggregation.

The cycle actually explains the mechanism of insulin resistance. The more muscle fat is present, the more insulin is needed to move the glucose into the cells – AKA insulin resistance. [6] The intramyocellular lipid doesn’t inhibit the insulin to move the glucose into cells but requires a larger amount of insulin. This is the stage of metabolic syndrome or pre-type 2 diabetes, which that can last around 13 years until beta-cell dysfunction (when the pancreas cannot produce insulin) occurs, resulting in the diagnosis of type 2 diabetes.

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Scientific References

[1] Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes Guilherme A, Virbasius JV, Puri V, Czech MP. Nat Rev Mol Cell Biol. 2008 May;9(5):367-77. doi: 10.1038/nrm2391. Review. PMID: 18401346

[2] Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes. Björnholm M, Zierath JR Biochem Soc Trans. 2005 Apr; 33(Pt 2):354-7.

[3] Fung, Jason, The Diabetes Code, 2018, Kindle Edition, location 159. Fung, Jason, The Obesity Code, 2016, Kindle Edition, location 2502.

[4] The Randle cycle revisited: a new head for an old hat. Hue L, Taegtmeyer H. Am J Physiol Endocrinol Metab. 2009 Sep;297(3): E578-91. doi: 10.1152/ajpendo.00093.2009. Epub 2009 Jun 16. Review.PMID: 19531645. Université Catholique de Louvain and de Duve Institute, Hormone and Metabolic Research Unit, Brussels, Belgium.

[5] The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. RANDLE PJ, GARLAND PB, HALES CN, NEWSHOLME EA Lancet. 1963 Apr 13; 1(7285):785-9.

[6] Pathogenesis of Insulin Resistance in Skeletal Muscle, Muhammad A. Abdul-Ghani and Ralph A. DeFronzo. Division of Diabetes, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA Received 7 December 2009; Accepted 20 January 2010.