Systemic lipolysis promotes physiological fitness in Drosophila melanogaster

Shang, Linshan; Aughey, E.; Kim, Hui‐Seon; Heden, Timothy D.; Wang, Lu; Najt, Charles P.; Esch, Nicholas; Brunko, Sophia; Abrahante, Juan; Macchietto, Marissa; Mashek, Mara T.; Fairbanks, Todd; Promislow, Daniel; Neufeld, Thomas; Mashek, Douglas G.

doi:10.18632/aging.204251

Cited by 8 publications

(3 citation statements)

References 61 publications

(76 reference statements)

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“…In Drosophila , lacking both maternal and zygotic Bmm activity causes embryonic lethality and embryos produced by Bmm-deficient female flies with WT males hatched nearly 40% [ 15 ]. Overexpression of Bmm robustly increased fecundity in female flies [ 33 ] and accumulation of lipids in ovary is essential for oogenesis [ 7 ]. Our results showed that loss-of-BmBmm activity caused reduced egg production and complete infertility in female silkworms due to TG deficiency.…”

Section: Discussionmentioning

confidence: 99%

Lipid homeostasis is essential for oogenesis and embryogenesis in the silkworm, Bombyx mori

Yang,

Xu,

et al. 2024

Cell. Mol. Life Sci.

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Reproduction, a fundamental feature of all known life, closely correlates with energy homeostasis. The control of synthesizing and mobilizing lipids are dynamic and well-organized processes to distribute lipid resources across tissues or generations. However, how lipid homeostasis is precisely coordinated during insect reproductive development is poorly understood. Here we describe the relations between energy metabolism and reproduction in the silkworm, Bombyx mori, a lepidopteran model insect, by using CRISPR/Cas9-mediated mutation analysis and comprehensively functional investigation on two major lipid lipases of Brummer (BmBmm) and hormone-sensitive lipase (BmHsl), and the sterol regulatory element binding protein (BmSrebp). BmBmm is a crucial regulator of lipolysis to maintain female fecundity by regulating the triglyceride (TG) storage among the midgut, the fat body, and the ovary. Lipidomics analysis reveals that defective lipolysis of females influences the composition of TG and other membrane lipids in the BmBmm mutant embryos. In contrast, BmHsl mediates embryonic development by controlling sterol metabolism rather than TG metabolism. Transcriptome analysis unveils that BmBmm deficiency significantly improves the expression of lipid synthesis-related genes including BmSrebp in the fat body. Subsequently, we identify BmSrebp as a key regulator of lipid accumulation in oocytes, which promotes oogenesis and cooperates with BmBmm to support the metabolic requirements of oocyte production. In summary, lipid homeostasis plays a vital role in supporting female reproductive success in silkworms.

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Section: Discussionmentioning

confidence: 99%

Lipid homeostasis is essential for oogenesis and embryogenesis in the silkworm, Bombyx mori

Yang,

Xu,

et al. 2024

Cell. Mol. Life Sci.

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“…Further overexpression of ATGL-1 (homolog of ATGL) extends the lifespan in C. elegans while the reduction of ATGL-1 function suppresses the longevity of the long-lived mutants eat-2 and daf-2 57,58 . Similarly, overexpression of brummer (bmm, the major TG hydrolase in Drosophila) improved several healthspan outcomes like fertility, locomotion, mitochondrial function, and oxidative metabolism in Drosophila 59 . Our present studies support these previous findings in lower organisms and show that lipolytic stimulation using β3-AR agonists promotes metabolic health in aged mice.…”

Section: Discussionmentioning

confidence: 99%

The metabolic benefits of thermogenic stimulation are preserved in aging

Natarajan,

Plakkot,

Tiwari

et al. 2024

Preprint

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Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the US (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1-independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose-dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3-AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Our study provides foundational evidence for targeting adipose thermogenesis to improve age-related metabolic dysfunction.

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“…Additionally, when bmm is suppressed across all tissues or metabolic speci c tissues through RNA interference, it results in a short lifespan of Drosophila (Nazario-Yepiz et al 2021). On the other hand, overexpression of bmm leads to a reduction in the size of lipid droplets, whereas a de ciency in bmm increases triacylglycerol (TAG) storage, leading to obesity and a reduction in lifespan (Shang et al 2022). At rst sight it is challenging to judge how the activity of bmm could in uence lifespan, but there exists a possible scheme for its action.…”

Section: Discussionmentioning

confidence: 99%

Berberis vulgaris L. extract supplementation exerts regulatory effects on the lifespan and healthspan of Drosophila through its antioxidant activity

Golubev,

Platonova,

Zemskaya

et al. 2023

Preprint

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Worldwide aging population continues to increase, so the concept of healthy longevity medicine has become increasingly significant in modern society. Berberis vulgaris L. fruits serve as a functional food supplement with a high concentration of bioactive compounds, which offer numerous health-promoting benefits. The goal of this study was to investigate the geroprotective effect of Berberis vulgaris L. extract. Here we show that extract of Berberis vulgaris L. can, depending on concentrate, increase lifespan up to 6%, promote healthspan (stress resistance up to 35%, locomotor activity up to 25%, integrity of the intestinal barrier up to 12%, metabolic rate up to 5%) of Drosophila melanogaster (in vitro) and exhibits antioxidant (using red blood cell tests) and antiglycation activity (using glycation of bovine serum albumin) (in vitro). In addition to this, the extract does not exhibit cytotoxic properties in vitro, unlike the well-known polyphenolic compound quercetin. qRT-PCR revealed the involvement of metabolic, heat shock response and lipid metabolism genes in the observed effects.

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Systemic lipolysis promotes physiological fitness in Drosophila melanogaster

Cited by 8 publications

References 61 publications

Lipid homeostasis is essential for oogenesis and embryogenesis in the silkworm, Bombyx mori

Lipid homeostasis is essential for oogenesis and embryogenesis in the silkworm, Bombyx mori

The metabolic benefits of thermogenic stimulation are preserved in aging

Berberis vulgaris L. extract supplementation exerts regulatory effects on the lifespan and healthspan of Drosophila through its antioxidant activity

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