ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Endocrinology of Aging
This article is part of the Research TopicSex Differences in AgingView all articles
Surgical Removal of Visceral Adipose Tissue has Therapeutic Benefit in Male APPNL-F Mice
Provisionally accepted
Samuel A McfaddenYimin FangKathleen QuinnMackenzie R PeckJenelle E ChapmanTiarra Hill
Andrzej Bartke
Erin Rutherford Hascup
Kevin Nicholas Hascup*- Southern Illinois University School of Medicine, Springfield, United States
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Purpose: Visceral white adipose tissue (vWAT) accumulation causes systemic inflammation, insulin resistance, metabolic syndrome, and senescent cell accumulation that are risk factors for Alzheimer’s disease (AD). Visceral fat removal (VFR) improves metabolism and reduces pro-inflammatory cytokines. We hypothesized that VFR removal in AD mice would improve metabolism and cognition. Methods: Male and female APPNL-F mice underwent sham or vWAT surgical resection (periovarian or epididymal and perirenal) at 4 (pre-symptomatic) and 16 (symptomatic) months of age to understand interventional and therapeutic effects, respectively. At 18 months of age, glucose metabolism and novel object recognition (NOR) memory were assayed followed by assessment of body composition and tissue-specific markers of metabolism, cell senescence, inflammation, or amyloid accumulation. Results: Male and female APPNL-F mice showed distinct VFR responses. In pre-symptomatic males, increased vWAT lipolysis and hepatic lipogenesis led to ectopic liver lipid accumulation, with reduced adiponectin and leptin, elevated visfatin, and impaired glucose metabolism. Symptomatic males showed reduced vWAT lipogenesis, enhanced hepatic lipolysis, glycolysis, and glycogenesis, lowering liver lipids and improving insulin sensitivity. Only symptomatic males improved NOR, linked to elevated hippocampal learning and memory markers. Female vWAT reaccumulation was due to increased lipogenesis and lower lipolysis. Pre-symptomatic females had lower hepatic lipogenesis, while glycolysis and glycogenesis declined with disease progression. Hippocampal senescence and inflammation were elevated early in the disease that persisted symptomatically. Conclusions: Sex-specific differences in glucose and lipid metabolism and lipid accumulation underlie the divergent responses to VFR in APPNL-F mice, with symptomatic males showing the only beneficial outcomes in metabolism and cognition.
Keywords: Alzheimer's disease, cell senescence, Glucose and lipid metabolism, Inflammation, Lipectomy, visfatin, white adipose tissue
Received: 07 Aug 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Mcfadden, Fang, Quinn, Peck, Chapman, Hill, Bartke, Hascup and Hascup. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kevin Nicholas Hascup
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