Adiponectin and resistin modulate the progression of Alzheimer´s disease in a metabolic syndrome model

Front Endocrinol (Lausanne). 2023 Sep 4:14:1237796. doi: 10.3389/fendo.2023.1237796. eCollection 2023.

Abstract

Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related brain diseases, including Alzheimer's disease (AD). However, the underlying mechanism explaining the link between MetS and brain function is poorly understood. Among the possible mediators are several adipose-derived secreted molecules called adipokines, including adiponectin (ApN) and resistin, which have been shown to regulate brain function by modulating several metabolic processes. To investigate the impact of adipokines on MetS, we employed a diet-induced model to induce the various complications associated with MetS. For this purpose, we administered a high-fat diet (HFD) to both WT and APP/PSN1 mice at a pre-symptomatic disease stage. Our data showed that MetS causes a fast decline in cognitive performance and stimulates Aβ42 production in the brain. Interestingly, ApN treatment restored glucose metabolism and improved cognitive functions by 50% while decreasing the Aβ42/40 ratio by approximately 65%. In contrast, resistin exacerbated Aβ pathology, increased oxidative stress, and strongly reduced glucose metabolism. Together, our data demonstrate that ApN and resistin alterations could further contribute to AD pathology.

Keywords: Alzheimer´s disease; adiponectin; glucose metabolism; obesity; resistin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Adiponectin
  • Alzheimer Disease* / etiology
  • Animals
  • Glucose
  • Metabolic Syndrome*
  • Mice
  • Obesity
  • Resistin

Substances

  • Adiponectin
  • Resistin
  • Adipokines
  • Glucose

Grants and funding

This work was supported by grants from the Basal Center of Excellence in Aging and Regeneration (CONICYT-AFB 170005) to NI, FONDECYT (no. 11160651) to PC. We also thank the Sociedad Química y Minera de Chile (SQM) for the special grants “The Role of K+ on Hypertension and Cognition”, “The Role of Lithium in Human Health and Disease”, and “Fondo interdisciplina del departamento Ciencias de la salud, P. Universidad Católica de Chile" to CM-O, and the Puente Fund of the Universidad de O’Higgins.