The Role of Leptin and Adiponectin in Obesity-Associated Cognitive Decline and Alzheimer’s Disease

Abstract

Cross-talk between adipose tissue and central nervous system (CNS) underlies the increased risk of obese people to develop brain diseases such as cognitive and mood disorders. Detailed mechanisms for how peripheral changes caused by adipose tissue accumulation in obesity impact the CNS to cause brain dysfunction are poorly understood. Adipokines are a large group of substances secreted by the white adipose tissue to regulate a wide range of homeostatic processes including, but not limited to, energy metabolism and immunity. Obesity is characterized by a generalized change in the levels of circulating adipokines due to abnormal accumulation and dysfunction of adipose tissue. Altered adipokine levels underlie complications of obesity as well as the increased risk for the development of obesity-related comorbidities such as type 2 diabetes, cardiovascular and neurodegenerative diseases. Here, we review the literature for the role of adipokines as key mediators of the communication between periphery and CNS in health and disease. We will focus on the actions of leptin and adiponectin, two of the most abundant and well studied adipokines, in the brain, with particular emphasis on how altered signaling of these adipokines in obesity may lead to cognitive dysfunction and augmented risk for Alzheimer’s disease. A better understanding of adipokine biology in brain disorders may prove of major relevance to diagnostic, prevention and therapy.

Obesity ‑ a risk factor for increased COVID‑19 prevalence, severity and lethality (Review)

“…obesity-induced adipokine production such as leptin /adiponectin ratio increases insulin resistance in type 2 diabetes, resulting in inability to feel and detect satiety leptin in the arcuate nucleus of mediobasal hypothalamus (78). Moreover, adverse effects are evident, despite high energy stores, on hunger, food energy use, physical exercise and energy balance as well as on hippocampus-mediated deficit in learning and memory functions (79). Furthermore, the prolonged iFn responses during persistent chronic inflammation and obesogenesis comprise reciprocal causality between virus susceptibility and obesity (80).…”

Neurocognitive Inhibitory Control Ability Performance and Correlations with Biochemical Markers in Obese Women

“…There is a possible explanation to account for the pattern of the findings on this topic. Adiponectin acts as an insulin-sensitizing hormone in muscle and liver, and lower levels of adiponectin further contribute to peripheral insulin resistance in obesity [75,76]. The adiponectin/leptin ratio is a functional biomarker of adipose tissue inflammation [77] and a good indicator of a dysfunctional adipose tissue, which may be a useful estimator of obesity and metabolic syndrome [77].…”

Tetrahydrocannabinolic Acid a (THCA-A) Reduces Adiposity and Prevents Metabolic Disease Caused by Diet-Induced Obesity

“…Obesity has reached pandemic proportions worldwide, with more than 650 million obese 95 and nearly 2 billion people being overweighed (6). Obesity is a major risk factor for the development of multiple diseases, including prominently cardiovascular and metabolic disorders, such as type-2 diabetes and metabolic syndrome (MetS) (7, 8), but also respiratory, osteoarticular, cognitive, reproductive and oncologic pathologies (9)(10)(11)(12). The basis for the multi-organ alterations seen in obesity remains unfolded (13), but the state of chronic, low-100 grade inflammation commonly associated to this condition is considered a major contributing factor (11).…”

“…The basis for the multi-organ alterations seen in obesity remains unfolded (13), but the state of chronic, low-100 grade inflammation commonly associated to this condition is considered a major contributing factor (11). This is reflected by the increased concentrations of white adipose tissue-derived pro-inflammatory cytokines (TNF-α, IL-6, leptin) and the antiparallel decrease of antiinflammatory signals, as adiponectin, commonly observed in obesity (12,14,15). Additional hormonal perturbations, e.g., of gastro-intestinal factors, such as ghrelin and GLP-1 (16), as 105 well as the ectopic deposition of fat, mostly in the liver (i.e., steatosis), which defines a state of lipotoxicity (17), contribute also to the worsening of the metabolic profile of obese 6 patients.…”