Adiponectin and Cognitive Decline

Abstract

Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Initially, it was thought that the main role was only the metabolism control. Later, ADPN receptors were also found in the central nervous system (CNS). In fact, the receptors AdipoR1 and AdipoR2 are expressed in various areas of the brain, including the hypothalamus, hippocampus, and cortex. While AdipoR1 regulates insulin sensitivity through the activation of the AMP-activated protein kinase (AMPK) pathway, AdipoR2 stimulates the neural plasticity through the activation of the peroxisome proliferator-activated receptor alpha (PPARα) pathway that inhibits inflammation and oxidative stress. Overall, based on its central and peripheral actions, ADPN appears to have neuroprotective effects by reducing inflammatory markers, such as C-reactive protein (PCR), interleukin 6 (IL6), and Tumor Necrosis Factor a (TNFa). Conversely, high levels of inflammatory cascade factors appear to inhibit the production of ADPN, suggesting bidirectional modulation. In addition, ADPN appears to have insulin-sensitizing action. It is known that a reduction in insulin signaling is associated with cognitive impairment. Based on this, it is of great interest to investigate the mechanism of restoration of the insulin signal in the brain as an action of ADPN, because it is useful for testing a possible pharmacological treatment for the improvement of cognitive decline. Anyway, if ADPN regulates neuronal functioning and cognitive performances by the glycemic metabolic system remains poorly explored. Moreover, although the mechanism is still unclear, women compared to men have a doubled risk of developing cognitive decline. Several studies have also supported that during the menopausal transition, the estrogen reduction can adversely affect the brain, in particular, verbal memory and verbal fluency. During the postmenopausal period, in obese and insulin-resistant individuals, ADPN serum levels are significantly reduced. Our recent study has evaluated the relationship between plasma ADPN levels and cognitive performances in menopausal women. Thus, the aim of this review is to summarize both the mechanisms and the effects of ADPN in the central nervous system and the relationship between plasma ADPN levels and cognitive performances, also in menopausal women.

Adiponectin-mimetic novel nonapeptide rescues aberrant neuronal metabolic-associated memory deficits in Alzheimer’s disease

“…Adiponectin activates AdipoR1 and prevents neuroinflammation and shows protective activities in various metabolic disorders. Hence, adipokines and their receptors, particularly adiponectin and its mimetic peptides via AdipoR1 activation, represent an emerging, novel and attractive potential therapeutic target for the prevention of AD and other neuropathological disorders [ 14 – 16 , 21 , 35 – 37 , 69 – 73 ]. However, adipokines, particularly adiponectin and its receptor, should be thoroughly monitored for translation-based studies because of recent findings and epidemiological studies that reported that an excess adiponectin level is associated with lethal effects, such as circulatory disorders (chronic heart failure & chronic kidney failure), as well as other undesirable effects, such as weight loss, low skeletal muscle mass/density, and physical functioning impairment, which ultimately lead to morbidity and mortality [ 26 – 31 ].…”

Protective effect of fenofibrate against high‐fat–high‐fructose diet induced non‐obese NAFLD in rats

“…Adiponectin (ADPN) is a plasma protein that belongs to the complement 1q family, and it is secreted by adipose tissue [45]. ADPN has pleiotropic effects, such as antidiabetic effects, increased insulin sensitivity of target organs [46], anti‐inflammatory and anti‐atherogenic properties [47].…”

Case Report: Concurrent Resistance and Aerobic Training Regulate Adiponectin Expression and Disease Severity in Multiple Sclerosis: A Case Study

“…Indeed, our MS patient had an EDSS score of 4.5 at baseline and reported a decrease of 0.5 after 4 months of training, which do not increase after 6 months of follow-up. Growing evidence has shown the beneficial influence of exercise on humans ( Liu et al, 2019 ; Rizzo et al, 2020 ); besides cardiometabolic positive effects, physical activity acts also on brain health, reducing the risk of neurodegenerative diseases as dementia ( Hamer and Chida, 2009 ; Liu et al, 2019 ). In MS, physical activity not only reduces the incidence of the disease but has also disease-modifying effects ( Dalgas et al, 2019 ; Grazioli et al, 2019b ) and our data seems to confirm that exercise decreases clinical severity.…”