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Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice

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Abstract

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging — the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs. This suggests an altered profile of factors produced in visceral fat in the absence of GH, indicating a unique interplay between adipose tissue function and hormonal influences in these models. Our aim was to analyze the gene expression related to lipid and glucose metabolism, insulin pathways, inflammation, thermoregulation, mitochondrial biogenesis, and epigenetic regulation in the visceral (perirenal and epididymal) adipose tissue of Ames dwarf and normal mice. Our findings reveal an upregulation in the expression of key genes such as Lpl, Adrβ3, Rstn, Foxo1, Foxo3a, Irs1, Cfd, Aldh2, Il6, Tnfα, Pgc1α, Ucp2, and Ezh2 in perirenal and Akt1, Foxo3a, PI3k, Ir, Acly, Il6, Ring1a, and Ring 1b in epididymal fat in df/df mice. These results suggest that the longevity phenotype in Ames dwarfs, which is determined by peripubertal GH/IGF-1 levels, may also involve epigenetic reprogramming of adipose tissue influenced by hormonal changes. The increased expression of genes involved in metabolic regulation, tumor suppression, mitochondrial biogenesis, and insulin pathways in Ames dwarf mice highlights potentially beneficial aspects of this model, opening new avenues for understanding the molecular underpinnings of longevity and aging.

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Funding

This work was supported by the National Science Centre, Poland (2016/21/B/NZ4/03192) (grant no. 507/1–168–02/507–10–105 of the Medical University of Lodz, Poland) (Adam Gesing). Andrea Lehoczki was supported by project no. TKP2021-NKTA-47, implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme; by funding through the National Cardiovascular Laboratory Program (RRF-2.3.1–21-2022–00003) provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund.

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  1. Department of Endocrinology of Ageing, Medical University of Lodz, Lodz, Poland

    Agnieszka Zaczek & Adam Gesing

  2. Department of Paediatric Endocrinology, Medical University of Lodz, Lodz, Poland

    Andrzej Lewiński

  3. Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland

    Andrzej Lewiński & Małgorzata Karbownik-Lewińska

  4. Department of Public Health, Semmelweis University, Budapest, Hungary

    Andrea Lehoczki

  5. Doctoral School, Health Sciences Program, Semmelweis University, Budapest, Hungary

    Andrea Lehoczki

  6. Department of Haematology and Stem Cell Transplantation, National Institute for Haematology and Infectious Diseases, South Pest Central Hospital, 1097, Budapest, Hungary

    Andrea Lehoczki

Authors
  1. Agnieszka Zaczek
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  2. Andrzej Lewiński
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  3. Małgorzata Karbownik-Lewińska
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  4. Andrea Lehoczki
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  5. Adam Gesing
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Correspondence to Adam Gesing.

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Zaczek, A., Lewiński, A., Karbownik-Lewińska, M. et al. Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice. GeroScience (2024). https://doi.org/10.1007/s11357-024-01131-1

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  • DOI: https://doi.org/10.1007/s11357-024-01131-1

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