Adipobiology of the brain: from brain diabetes to adipose Alzheimer‘s disease

Recent studies suggest that diabetes mellitus affects multiple cognitive functions including expression of amyloid precursor protein (APP), amyloid-β (Aβ) peptide and hyperphosphorylated Tau - molecular signatures of Alzheimer`s disease (AD). Further, the administration of streptozotocin (STZ), a well known experimental model for diabetes, induces brain insulin resistance and cognitive alterations resembling those in AD patients. Thus the STZ treatment became a new experimental tool in studying AD, which is increasingly evaluated as type 3 diabetes. Accordingly, the concept of brain diabetes was introduced. We have reported that STZ-induced diabetes is associated with changes in nerve growth factor (NGF) levels in both pancreas and brain (Arch Ital Biol 2007; 145:87-97). Intriguingly, data of an extraneuronal production of both APP and Aβ peptides including in the adipose tissue were reported. In the last 20 years, adipose tissue and its endocrine secretory proteins (adipokines) take center stage in studying cardiometabolic (including diabetes) and neurodegenerative (including AD) diseases, both associated with adipose-derived neurometabotrophic factors (e.g. NGF, BDNF, leptin, adiponectin, betatrophin, neudesin, progranulin, irisin) (World J Pharmacol 2013; 2: 92-99). Altogether, our hypothesis of adipose tissue as a third brain (Obesity Metab 2009; 5: 94-96; Cell Biol Int 2010; 34:1051-1053), herein referred to as adipose AD, may sound more plausible at present. However, the major questions which remain to be answered are: (i) may AD pathology spread from the adipose tissue to the brain, and (ii) may AD be considered a neurometabolic disease.