Dataset Information

Association of cognition with leptin and vascular endothelial growth factor in individuals with type 2 diabetes mellitus.

ABSTRACT:

Objective

The 10-year intensive lifestyle intervention (ILI) of the Look AHEAD study left a legacy of relative deficits in cognitive function among participants who entered the clinical trial with obesity or a history of cardiovascular disease. We hypothesized that altered levels of two weight-sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), accounted for this concerning finding.

Methods

Serum leptin and VEGF concentrations were determined in 1,279 Look AHEAD participants at baseline, proximal to cessation of the interventions (Epoch 1), and an average of 4 years later (Epoch 2). Up to four standardized assessments of attention, executive function, and memory were collected during follow-up. Mixed effects models were used to assess relative differences in leptin and VEGF concentrations between intervention groups and whether these accounted for changes in cognitive composite scores.

Results

ILI and diabetes support and education differences in VEGF, but not leptin, concentrations varied depending on baseline history of cardiovascular disease and obesity, but neither leptin nor VEGF concentrations accounted for the relative decrements in cognitive function in participants assigned to ILI.

Conclusions

Alterations in two weight-sensitive proangiogenic cytokines did not account for the long-term adverse effects of ILI on cognitive function among adults with diabetes and either obesity or cardiovascular disease.

SUBMITTER: Espeland MA

PROVIDER: S-EPMC9420754 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of cognition with leptin and vascular endothelial growth factor in individuals with type 2 diabetes mellitus.

Espeland Mark A MA Evans Joni K JK Carmichael Owen O Luchsinger Jose A JA Marcovina Santica M SM Neiberg Rebecca R Johnson Karen C KC Kahn Steven E SE Hayden Kathleen M KM

Obesity (Silver Spring, Md.) 20220803 9

<h4>Objective</h4>The 10-year intensive lifestyle intervention (ILI) of the Look AHEAD study left a legacy of relative deficits in cognitive function among participants who entered the clinical trial with obesity or a history of cardiovascular disease. We hypothesized that altered levels of two weight-sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), accounted for this concerning finding.<h4>Methods</h4>Serum leptin and VEGF concentrations were determined i ...[more]

PMID: 35920161

Similar Datasets

Project description:BackgroundThe adipocyte-derived hormone leptin influences the behaviour of a wide range of cell types and is now recognised as a pro-angiogenic and pro-inflammatory factor. In the vasculature, these effects are mediated in part through its direct leptin receptor (ObRb)-driven actions on endothelial cells (ECs) but the mechanisms responsible for these activities have not been established. In this study we sought to more fully define the molecular links between inflammatory and angiogenic responses of leptin-stimulated human ECs.Methodology/principal findingsImmunoblotting studies showed that leptin increased cyclo-oxygenase-2 (COX-2) expression (but not COX-1) in cultured human umbilical vein ECs (HUVEC) through pathways that depend upon activation of both p38 mitogen-activated protein kinase (p38(MAPK)) and Akt, and stimulated rapid phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) on Tyr(1175). Phosphorylation of VEGFR2, p38(MAPK) and Akt, and COX-2 induction in cells challenged with leptin were blocked by a specific leptin peptide receptor antagonist. Pharmacological inhibitors of COX-2, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and p38(MAPK) abrogated leptin-induced EC proliferation (assessed by quantifying 5-bromo-2'-deoxyuridine incorporation, calcein fluorescence and propidium iodide staining), slowed the increased migration rate of leptin-stimulated cells (in vitro wound healing assay) and inhibited leptin-induced capillary-like tube formation by HUVEC on Matrigel. Inhibition of VEGFR2 tyrosine kinase activity reduced leptin-stimulated p38(MAPK) and Akt activation, COX-2 induction, and pro-angiogenic EC responses, and blockade of VEGFR2 or COX-2 activities abolished leptin-driven neo-angiogenesis in a chick chorioallantoic membrane vascularisation assay in vivo.Conclusions/significanceWe conclude that a functional endothelial p38(MAPK)/Akt/COX-2 signalling axis is required for leptin's pro-angiogenic actions and that this is regulated upstream by ObRb-dependent activation of VEGFR2. These studies identify a new function for VEGFR2 as a mediator of leptin-stimulated COX-2 expression and angiogenesis and have implications for understanding leptin's regulation of the vasculature in both non-obese and obese individuals.

Dataset Information

Association of cognition with leptin and vascular endothelial growth factor in individuals with type 2 diabetes mellitus.

Objective

Methods

Results

Conclusions

Publications

Association of cognition with leptin and vascular endothelial growth factor in individuals with type 2 diabetes mellitus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets