Inflammation and Insulin, and IGF-1 Resistance: The Link Between Obesity and Neurodegeneration.
by Elizabeth Ho
Obesity is possibly linked to neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s disease. However, not many people know obesity can lead to neurodegenerative diseases. In Spieiman, L. et al., 2014, obesity can lead to insulin resistance to neurodegeneration.
The root cause of the problem is obesity, which causes metabolic syndrome and neurodegeneration. This leads to decrease insulin resistance and Insulin-like growth factor-1 (IGF-1) levels. Insulin is for balancing and maintaining blood glucose levels. Insulin is produced by pancreatic β-cells to regulate gluconeogenesis, increase glycogen synthesis and promote lipid synthesis. When insulin secretion fails to compensate for insulin, that is responsible for development of type II diabetes. For example, our bodies are just like our bank account, high insulin means to make deposit more money in our account “well-fed state” or low insulin means to with little money in the account “broke state”. In “well-fed state”, we have enough storing energy to consume. On the other hand], “broke state”, we are in survival mode so we rely on our stores of food energy.
What is insulin resistance/IGF-resistance?
Obesity is a leading factor of insulin and IGF-resistance along with chronic inflammation. Inflammation is caused by innate response of survival to fight off infection or injury of the body and initiate of the immune system response. Obesity leads to a low-grade inflammatory response to the adipose tissue so setting these cascades of actions by immune cells. These cascades are responsible for the overstimulation to cytokines which leads to insulin resistance and IGF-1 resistance. IGF-1 is a metabolic and anabolic hormone. Function of IGF-1. IGF-1 works as a cell stimulant for mitosis, survival stimulant, apoptosis/cell death inhibitor, as well as inducing fatty acid degradation and glucose uptake by myokines. IGF-1 resistance impacted brain development, maturation and function. IGF-1 deficiency is caused by age and nutritional status. IGF-1 secretion compels adequate nutrition or it cannot occur, which leads to its resistance. Malnourishment and obesity also cause IGF-1 resistance because of the insufficient ability to secrete IGF-1. Insulin and IGF-1 resistance caused weakening of neuroprotective by pro-inflammatory cytokines (IL-6).
Two Factors Link to Obesity and Neurodegeneration:
- Proinflammatory Cytokines
- Insulin/IGF-1 Resistance
Use induced insulin/IGF-1 resistance contribution to Huntington’s disease (HD) obesity pathology as an example to explain how obesity leads to neurodegeneration. Obesity acts as a risk factor of HD. IL-6 is an interleukin/ a cytokine which acts as a pro-inflammatory and anti-inflammatory, and involve inflammation. Obesity is the root of increasing IL-6 level. Adipocytes are also known as a source of IL-6. Adipocytes secrete the anti-inflammatory, which is inversely associated with adiposity. People who are obese have lower circulating levels of this anti-inflammatory signal. The chronic low-grade inflammatory state of obesity may contribute to HD, via the secretion of specific mediators. Obesity decreases insulin sensitivity lead to the release of free fatty acids to upregulate IL-6. However, IL-6 has been implicated in exacerbation of neuroinflammation. Obesity also is a leading risk of decreasing insulin resistance, IGF-1. IGF-1 also acts as a growth factor, cell survival stimulant, and apoptosis inhibitor. Thus, low IGF-1 leads to decrease regulation of HTT genes, it expanded CAG repeat in the Huntington (HTT) gene, Mutant Htt (mHTT) features an increased number of glutamines. The decrease in IGF-1 concentration can increase signaling errors that have been associated with pathological states as HD.
Not many people would treat the root cause of obesity but treating the problems caused by obesity rather than obesity itself. We often hear ‘exercise more’ when it comes to weight loss. In So, et al. is well-established the link between exercise-induced myokines in health and metabolic diseases. Myokines release from myocytes (muscle cells) during exercise. The study has shown myokines involved regulating metabolism and homeostasis.
References:
Spielman, L. J., Little, J. P., & Klegeris, A. (2014). Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration. Journal of Neuroimmunology,273(1–2), 8–21. doi:10.1016/j.jneuroim.2014.06.004
So, B., Kim, H., Kim, J., & Song, W. (2014). Exercise-induced myokines in health and metabolic diseases. Integrative Medicine Research,3(4), 172–179. doi:10.1016/j.imr.2014.09.007
