Insulin Resistance Contributes to Neuroinflammation, Cognitive Decline and Brain Senescence in Congenic Obese LA/Ntul//-cp Rats | Chapter 9 | Advancement and New Understanding in Medical Science Vol. 7

Search for a suitable an animal model may prove to be more productive to determine if insulin resistance and its direct metabolic sequelae might be significant co-contributors to the neuronal declines that occur in NIDDM, obesity, and progression of dementia conditions. The burgeoning prevalence of obesity and overweight conditions from the age of adolescence and throughout the lifespan has reached epidemic proportions in industrialized nations throughout the globe. One of the most prevalent findings in obesity is the emergence of insulin resistance, which is linked to both a persistent inflammatory state and systemic hypoxia in adipose tissue. Insulin resistance impacts several aspects of substrate oxidation and oxidative free radical production in brain and somatic tissues, and it is likely that adipose tissue depots are the source of cytokine-linked chronic inflammation. In studies with aging congenic lean and obese rats chronic hyperinsulinemia and brain shrinkage has now been reported, albeit it in the absence of Type 2 diabetes (NIDDM), hypertension (HTN) or other comorbidities, thereby suggesting that aspects of disordered substrate metabolism including insulin resistance as commonly observed in obesity may be a key contributory factor in the development of a neuroinflammatory linked brain shrinkage with accompanying decreases in brain mass, protein and DNA content, and which were further compromised when fed an isocaloric high vs. a low glycemic insulinogenic diet containing sucrose vs. cornstarch respectively. These findings imply that in this strain of obese rats, chronic insulin resistance due to obesity, which is at least partially caused by dietary variables, is a plausible independent risk factor in the development of neuroinflammation, DNA damage, brain shrinkage, and neural senescence.

Author(s) Details:

Orien L. Tulp,
Colleges of Medicine and Graduate Studies, University of Science Arts and Technology, Montserrat, British West Indies, MSR1110 and the Einstein Medical Institute, North Palm Beach, FL 33409, USA.

Please see the link here: https://stm.bookpi.org/ANUMS-V7/article/view/13427