Partial removal of visceral epididymal white adipose tissue in obese Ldlr-/-.Leiden mice impacts adipokine secretion, plasma free fatty acids, and improves cerebrovascular health

作者：Florine Seidel, Martine C. Morrison, Ilse A.C. Arnoldussen, Viviènne Verweij, Simon Ebert, Joline Attema, Christa de Ruiter, Wim van Duyvenvoorde, Jessica M. Snabel, Bram Geenen, Ayla Franco, Eveline Gart, Jürgen Bernhagen, Maximilian Wiesmann, Robert Kleemann, Amanda J. Kiliaan · 发表于：PLoS ONE · 年份：2025 · DOI：10.1371/journal.pone.0333024 · 被引用次数：2 · 研究领域：Adipose Tissue and Metabolism、Adipokines, Inflammation, and Metabolic Diseases、Cardiovascular Disease and Adiposity

Visceral white adipose tissue (WAT) dysfunction may contribute to obesity-related brain impairments but causal relationship has not been demonstrated. We herein investigated the impact of visceral epididymal WAT (eWAT) lipectomy on brain health and obesity-associated comorbidities (liver steatosis, atherosclerosis, WAT dysfunction) in obese Ldlr-/-.Leiden mice. High-fat diet (HFD)-fed obese mice underwent sham surgery or partial removal (~70%) of eWAT. A separate group of mice was kept on chow diet (control). Liver disease, atherosclerosis and three WAT depots were examined histologically, and WAT biopsies were also cultured ex vivo. Brain structure and function were monitored longitudinally using cognitive tests and neuroimaging, paralleled by histological analysis of brain pathology and hippocampal RNA-sequencing. In ex vivo WAT culture, the surgically removed eWAT portion secreted many adipokines and pro-inflammatory factors. Histological analyses at the end of the study showed that eWAT-lipectomy did not affect liver disease and atherosclerosis development, but reduced the number of severely hypertrophic adipocytes in the residual-eWAT. This was consistent with reduced secretion of adipokines (e.g., leptin, adiponectin) and pro-inflammatory mediators (e.g., PAI-1, MIP-1α/CCL3, IL-17) from the residual-eWAT in the ex vivo culturing experiments. Importantly, lipectomy alleviated HFD-induced adverse effects on hippocampal vasoreactivity, increased cortico-hippocampal (restin...