Apolipoprotein C3 and circulating mediators of preadipocyte proliferation in states of lipodystrophy

Brasil, Brandao Bruna; Sakaguchi, Masaji; Martins, Batista Thiago; Hu, Jiang; Nie, Song; A, Schepmoes Athena; BonDurant, Lucas; Marchand, François; Qian, Weijun; Rohit, Kulkarni; Ronald, Kahn C

doi:10.1016/j.molmet.2022.101572

Cited by 3 publications

(2 citation statements)

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“…To control for the acute and direct effects of tamoxifen treatment in islets, male C57Bl/6 mice aged 8–12 months were treated with the drug and with the vehicle. There were no significant differences in gene expression of key β-cell genes ( Figure 2C ), consistent with previous reports of a lack of effects of tamoxifen administration on glucose homeostasis ( 13 , 14 ).…”

Section: Resultssupporting

confidence: 92%

Decreased IGF1R attenuates senescence and improves function in pancreatic β-cells

et al. 2023

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IntroductionThe enhanced β-cell senescence that accompanies insulin resistance and aging contributes to cellular dysfunction and loss of transcriptional identity leading to type 2 diabetes (T2D). While senescence is among the 12 recognized hallmarks of aging, its relation to other hallmarks including altered nutrient sensing (insulin/IGF1 pathway) in β-cells is not fully understood. We previously reported that an increased expression of IGF1R in mouse and human β-cells is a marker of older β-cells; however, its contribution to age-related dysfunction and cellular senescence remains to be determined.MethodsIn this study, we explored the direct role of IGF1R in β-cell function and senescence using two independent mouse models with decreased IGF1/IGF1R signaling: a) Ames Dwarf mice (Dwarf +/+), which lack growth hormone and therefore have reduced circulating levels of IGF1, and b) inducible β-cell-specific IGF1R knockdown (βIgf1rKD) mice.ResultsCompared to Dwarf+/- mice, Dwarf+/+ mice had lower body and pancreas weight, lower circulating IGF1 and insulin levels, and lower IGF1R and p21Cip1 protein expression in β-cells, suggesting the suppression of senescence. Adult βIgf1rKD mice showed improved glucose clearance and glucose-induced insulin secretion, accompanied by decreased p21Cip1 protein expression in β-cells. RNA-Seq of islets isolated from these βIgf1rKD mice revealed the restoration of three signaling pathways known to be downregulated by aging: sulfide oxidation, autophagy, and mTOR signaling. Additionally, deletion of IGF1R in mouse β-cells increased transcription of genes important for maintaining β-cell identity and function, such as Mafa, Nkx6.1, and Kcnj11, while decreasing senescence-related genes, such as Cdkn2a, Il1b, and Serpine 1. Decreased senescence and improved insulin-secretory function of β-cells were also evident when the βIgf1rKD mice were fed a high-fat diet (HFD; 60% kcal from fat, for 5 weeks).DiscussionThese results suggest that IGF1R signaling plays a causal role in aging-induced β-cell dysfunction. Our data also demonstrate a relationship between decreased IGF1R signaling and suppressed cellular senescence in pancreatic β-cells. Future studies can further our understanding of the interaction between senescence and aging, developing interventions that restore β-cell function and identity, therefore preventing the progression to T2D.

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Section: Resultssupporting

confidence: 92%

Decreased IGF1R attenuates senescence and improves function in pancreatic β-cells

et al. 2023

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“…Committed preadipocytes arise from multipotent, gradually replicating mesenchymal progenitor cells and potentially circulating progenitors [ 81 – 83 ]. Preadipocytes also play critical immunological, proinflammatory, and hemostatic roles and express markers of the monocyte-macrophage lineage [ 84 – 86 ]. Their osteogenic potential is impaired with aging, whereas their adipogenic potential is maintained [ 87 , 88 ].…”

Section: Deterioration Of Stem Cell Reservoir In the Age-related Mili...mentioning

confidence: 99%

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function

Liu,

Lu,

Feng

2024

Cell Death Dis

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Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

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Anti-hyperlipidemic and antioxidant ability of HeShouWu (roots of Polygonum multiflorum Thunb.) and its complex formula

Huang,

Cheng,

Chan

et al. 2023

Arabian Journal of Chemistry

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Apolipoprotein C3 and circulating mediators of preadipocyte proliferation in states of lipodystrophy

Cited by 3 publications

References 57 publications

Decreased IGF1R attenuates senescence and improves function in pancreatic β-cells

Decreased IGF1R attenuates senescence and improves function in pancreatic β-cells

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function

Anti-hyperlipidemic and antioxidant ability of HeShouWu (roots of Polygonum multiflorum Thunb.) and its complex formula

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