Central Adiponectin Signaling – A Metabolic Regulator in Support of Brain Plasticity

Abstract

Brain plasticity and metabolism are tightly connected by a constant influx of peripheral glucose to the central nervous system in order to meet the high metabolic demands imposed by neuronal activity. Metabolic disturbances highly affect neuronal plasticity, which underlies the prevalent comorbidity between metabolic disorders, cognitive impairment, and mood dysfunction. Effective pro-cognitive and neuropsychiatric interventions, therefore, should consider the metabolic aspect of brain plasticity to achieve high effectiveness. The adipocyte-secreted hormone, adiponectin, is a metabolic regulator that crosses the blood-brain barrier and modulates neuronal activity in several brain regions, where it exerts neurotrophic and neuroprotective properties. Moreover, adiponectin has been shown to improve neuronal metabolism in different animal models, including obesity, diabetes, and Alzheimer’s disease. Here, we aim at linking the adiponectin’s neurotrophic and neuroprotective properties with its main role as a metabolic regulator and to summarize the possible mechanisms of action on improving brain plasticity via its role in regulating the intracellular energetic activity. Such properties suggest adiponectin signaling as a potential target to counteract the central metabolic disturbances and impaired neuronal plasticity underlying many neuropsychiatric disorders.

Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance

“…That increasing age is a risk factor is predictable, while the correlation with adropin supports our hypothesis. The 'adiponectin paradox' where high levels of a protein with neuroprotective properties associate with mild cognitive impairment has also been reported elsewhere 38 .…”

Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role

“…Moreover, as a consequence of stroke, the structural integrity of the BBB is affected and under inflammatory conditions, matrix metalloproteinases (MMPs) can degrade basal layer proteins, increasing the BBB’s permeability ( Zlokovic, 2006 ; Lakhan et al, 2013 ). LPS, SCFAs, adiponectin, vasoactive intestinal peptide (VIP), and some neurotransmitter precursors (e.g., 5-HTP) were more readily transported across the BBB to the brain due to increased BBB permeability ( Birdsall, 1998 ; Dogrukol-Ak et al, 2003 ; Nedorubov et al, 2019 ; Megur et al, 2020 ; Formolo et al, 2022 ; Zhao et al, 2022 ).…”

Proceedings from the Albert Charitable Trust Inaugural Workshop on ‘Understanding the Acute Effects of Exercise on the Brain’

“…These include myokines [114,115] such as VEGF [116] irisin [117][118][119] and Cathepsin B [30,[120][121][122] as well as the myometabolite lactate [98]. In addition, hepatokines (insulin-like growth factor ( [123], clusterin [124], glycerophosphoryl diester phosphodiesterase-like protein [125]), adipokines [126], and blood platelets [127] derived from runners have been shown to play a role in neural plasticity or cognition [128][129][130]. Conversely, an unhealthy, highfat and sugar diet can result in metabolic disturbances in the gut microbiome that impair learning and memory [131].…”