Obesity and brain inflammation: a focus on multiple sclerosis

Abstract

The increase in prevalence of obesity in industrialized societies is an indisputable fact. However, the apparent passive role played by adipocytes, in pathophysiological terms, has been gradually substituted by a metabolically active performance, relevant to many biochemical mechanisms that may contribute to a chronic low-grade inflammatory status, which increasingly imposes itself as a key feature of obesity. This chronic inflammatory status will have to be integrated into the complex equation of many diseases in which inflammation plays a crucial role. Multiple sclerosis (MS) is a chronic inflammatory condition typically confined to the central nervous system, and many work has been produced to find possible points of contact between the biology of this immune-mediated disease and obesity. So far, clinical data are not conclusive, but many biochemical features have been recently disclosed. Brain inflammation has been implicated in some of the mechanisms that lead to obesity, which has also been recognized as an important player in inducing some degree of immune dysfunction. In this review, we collected evidence that allows establishing bridges between obesity and MS. After considering epidemiological controversies, we will focus on possible shared mechanisms, as well as on the potential contributions that disease-modifying drugs may have on this apparent relationship of mutual interference.

Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity

“…Obesity is a chronic inflammatory process, during which immune cells such as myeloid and lymphoid cells infiltrate adipose tissue. The expression of inflammatory cytokines, such as IL-6 and TNF-, in adipose tissue is increased in obesity and is associated with inflammation in adipose tissue (37,38). Interestingly, when 3T3-L1 adipocytes were treated with IL-6 and TNF- together, ATX expression was upregulated to a significantly higher level compared with that found using IL-6 or TNF- alone (Fig.…”

Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

“…Newly diagnosed MS patients exhibit hyperinsulinemia and decreased insulin sensitivity (Penesova et al, 2015) suggesting that obesity is a potential risk factor for MS (Palavra et al, 2016). Treating underlying metabolic syndrome with classic anti-diabetic drugs such as metformin and pioglitazone ameliorates metabolic disturbances, reduces MRI-evident lesion frequency and dampens T-cell pro-inflammatory response in MS patients (Negrotto et al, 2016).…”

Weight control and physical exercise in people with multiple sclerosis: Current knowledge and future perspectives

“…In recent years, many studies have been conducted to explain the upstream mechanisms of inflammation. Numerous studies suggested that inflammation occurs as a consequence of weight gain, and the production and development of inflammation plays an important role in increasing CVD risk, including insulin resistance, glucose intolerance, dyslipidemia, and hypertension (42,43). Interestingly, obesity-induced inflammation is unique compared to other recorded inflammatory paradigms that involve tonic activation of the immune system.…”

“…including interleukin (IL)-6 and tumour necrosis factor (TNF)-α, especially from visceral fat, increases along with weight gain; unlike, anti-inflammatory mediators (i.e., IL-1B) are downregulated (43). Therefore, obesity stimulates inflammation and contributes to the initiation and progression of MS.…”