Van Dyken P, Lacoste B. Impact of Metabolic Syndrome on Neuroinflammation and the Blood-Brain Barrier. Front Neurosci. 2018;12:930.
Key Points:
a) Many external factors, such as cigarette smoking and low vitamin D levels, can affect the course of MS.
b) Patients and doctors also know that having other diseases can worsen MS. How this happens is often not clear.
c) One very common illness that can worsen MS is metabolic syndrome
d) Metabolic syndrome is a group of conditions that increases with age, and can affect up to 40% of older persons.
e) Metabolic syndrome consists of increased blood pressure, high blood sugar, excess body fat around the waist, and high cholesterol or triglyceride levels.
f) Metabolic syndrome increases the risk of developing Type II diabetes, heart disease and stroke.
g) Initial treatment of metabolic syndrome involves changes in diet, weight loss and regular exercise.
h) The blood brain barrier (BBB) separates the body’s circulating blood from brain tissue. It is relatively resistant to invasion by immune cells and to large molecules such as antibodies.
i) Because of the brain inflammation in MS there is a breakdown of the blood brain barrier, allowing easier entry of toxins, antibodies and immune cells into the brain.
j) The presence of other disease such as metabolic syndrome increases damage to the blood brain barrier by increasing inflammation throughout the body. This further damages the blood brain barrier, allowing even easier entry of potentially harmful immune cells, toxins and antibodies.
k) Healthcare providers treating persons with MS must have a holistic approach to treatment, focusing both on specific MS therapies and on the treatment of other illnesses, such as metabolic syndrome, that can worsen MS.
l) Understanding how other disease affect MS could lead to new MS-specific therapies.
Persons with MS, especially those with disabilities, may have increased difficulty maintaining good health. Fatigue, poor sleep, weakness, pain, depression, lack of accessibility, all can contribute to this, as can poor diet and economic issues. This article describes in detail how metabolic syndrome increases bodily levels of inflammation, which in turn results in greater dysfunction of a major protective mechanism of the central nervous system, the blood brain barrier.
The blood brain barrier is already impaired in MS, allowing easier entry of potentially harmful immune cells, toxins and antibodies. Comorbid conditions such as metabolic syndrome can further impair blood brain barrier function, leading to a worsening of a person’s MS. One of the risk factors for developing metabolic syndrome is a high fat diet. In experimental animals on a high fat diet, even before weight gain is noticed, there are signs of inflammation in a part of the brain called the hypothalamus, a region involved with, among other functions, energy, weight control, and the production of a hormone called leptin. Leptin regulates appetite and weight control, and also modulates inflammation. In addition, portions of the brain associated with memory function, such as the hippocampus, are affected with metabolic syndrome, at least in animal models of MS, resulting in impaired memory function.
High blood sugars similarly cause an inflammatory response, associated with increased permeability of the blood brain barrier, in particular a region of the central nervous system, the choroid plexus. High blood sugars also result in increased production of hormones such as VGEG and substances such as nitric oxide, both potentially harmful. Gut bacteria (the gut microbiome) also are affected, an important body region increasingly implicated in both susceptibility to MS and in affecting disease course.
In practical terms, too many neurologists spend much of their face-to-face patient time discussing treatment options and managing treatment side effects and efficacies rather than addressing other health issues. In that context, the above article should serve as a reminder that essential to the “holistic” care of persons with MS should be equal attention to life-style management that can significantly impact disease course. This includes adherence to a healthy diet, regular exercise within the limits imposed by a person’s MS, quitting cigarettes and vaping, and routine monitoring of weight, blood sugars and blood pressure.
Paper Abstract:
Metabolic syndrome, which includes diabetes and obesity, is one of the most widespread medical conditions. It induces systemic inflammation, causing far-reaching effects on the body that are still being uncovered. Neuropathologies triggered by metabolic syndrome often result from increased permeability of the blood-brain-barrier (BBB). The BBB, a system designed to restrict entry of toxins, immune cells, and pathogens to the brain, is vital for proper neuronal function. Local and systemic inflammation induced by obesity or type 2 diabetes mellitus can cause BBB breakdown, decreased removal of waste, and increased infiltration of immune cells. This leads to disruption of glial and neuronal cells, causing hormonal dysregulation, increased immune sensitivity, or cognitive impairment depending on the affected brain region. Inflammatory effects of metabolic syndrome have been linked to neurodegenerative diseases. In this review, we discuss the effects of obesity and diabetes-induced inflammation on the BBB, the roles played by leptin and insulin resistance, as well as BBB changes occurring at the molecular level. We explore signaling pathways including VEGF, HIFs, PKC, Rho/ROCK, eNOS, and miRNAs. Finally, we discuss the broader implications of neural inflammation, including its connection to Alzheimer's disease, multiple sclerosis, and the gut microbiome.