Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in
            <i>Drosophila</i>

Miao, T.; Kim, Jinoh; Kang, Ping; Fujiwara, Hideji; Hsu, Fong‐Fu; Bai, Hua

doi:10.1073/pnas.2212220119

Cited by 9 publications

(9 citation statements)

References 73 publications

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“…Because recent findings indicate that FAS is regulated post-transcriptionally by autoacetylation based on nutrient availability (Miao et al ., 2022), we chose to measure the activity level of fat body FAS activity rather than gene expression. Fat body FAS activity was assayed using a previously-described assay (Lu, Chuang and Hsu, 2017) with minor modifications.…”

Section: Methodsmentioning

confidence: 99%

Fat body lipogenic capacity in honey bee workers is affected by age, social role, and dietary protein

Scofield,

Amdam

2024

Preprint

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All organisms need to balance processes that consume energy against those that produce energy. With an increase in biological complexity over evolutionary time, regulation of this balance has become much more complex, resulting in specialization of metabolic tasks between organelles, cells, organs, and in the case of eusocial organisms, between the individuals who comprise the "superorganism." Exemplifying this, nurse honey bees maintain high abdominal lipids, while foragers have very low lipid stores, likely contributing to efficient performance of their social role, and thus to colony fitness. The proximate mechanisms responsible for these metabolic differences remain poorly understood. Here, we investigated the effects of age, age class, and dietary macronutrients on the abdominal activity of fatty acid synthase (FAS), the enzyme responsible for de novo synthesis of fatty acids. We found that FAS activity declines as bees age past peak nursing age. Feeding both nurses and foragers carbohydrates increased FAS activity compared with starved bee, but, whether fed or starved, nurses had much higher FAS activity than similarly treated foragers, implicating reduced lipid synthesis as one component of foragers' low lipid stores. Finally, we used artificial diets with different amounts of protein and fat to precociously induce low, forager-like FAS activity levels in nurse-age bees deprived of protein. We speculate that reduced protein appetite and consumption during the nurse-forager transition is responsible for suppressed lipid synthesis in foragers.

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Section: Methodsmentioning

confidence: 99%

Fat body lipogenic capacity in honey bee workers is affected by age, social role, and dietary protein

Scofield,

Amdam

2024

Preprint

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“…peroxisome proliferator-activated receptor-gamma coactivator-1β (also referred to as PGC-1β) as shown in Figure 3. [63][64][65][66] Upregulation of SREBP1c leads to FA production in HCC, which is caused by the Akt/mTOR signaling pathway that is activated by CD147. 66 The PI3K/ Akt signaling pathway regulates lipid metabolism in cancer cells.…”

Section: Fgl1 and Lipid Metabolic Reprogramming Of Tumor Cellsmentioning

confidence: 99%

Role of Fibrinogen-like Protein 1 in Tumor Recurrence Following Hepatectomy

Shafieizadeh,

Davoudi

et al. 2024

J Clin Transl Hepatol

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Partial hepatectomy is a first-line treatment for hepatocellular carcinoma. Within 2 weeks following partial hepatectomy, specific molecular pathways are activated to promote liver regeneration. Nevertheless, residual microtumors may also exploit these pathways to reappear and metastasize. Therapeutically targeting molecules that are differentially regulated between normal cells and malignancies, such as fibrinogen-like protein 1 (FGL1), appears to be an effective approach. The potential functions of FGL1 in both regenerative and malignant cells are discussed within the ambit of this review. While FGL1 is normally elevated in regenerative hepatocytes, it is normally downregulated in malignant cells. Hepatectomy does indeed upregulate FGL1 by increasing the release of transcription factors that promote FGL1, including HNF-1α and STAT3, and inflammatory effectors, such as TGF-β and IL6. This, in turn, stimulates certain proliferative pathways, including EGFR/Src/ERK. Hepatectomy alters the phase transition of highly differentiated hepatocytes from G0 to G1, thereby transforming susceptible cells into cancerous ones. Activation of the PI3K/Akt/mTOR pathway by FGL1 allele loss on chromosome 8, a tumor suppressor area, may also cause hepatocellular carcinoma. Interestingly, FGL1 is specifically expressed in the liver via HNF-1α histone acetylase activity, which triggers lipid metabolic reprogramming in malignancies. FGL1 might also be involved in other carcinogenesis processes such as hypoxia, epithelial-mesenchymal transition, immunosuppression, and sorafenib-mediated drug resistance. This study highlights a research gap in these disciplines and the necessity for additional research on FGL1 function in the described processes.

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“…Fly lines used in this study: yw R (a gift from Eric Rulifson); yw R ; FASN Flag ( Miao et al, 2022 ). Flies were maintained at 25 °C, 60% relative humidity, and a 12:12 h light/dark cycle.…”

Section: Materials and Reagentsmentioning

confidence: 99%

“…However, due to the low abundance of some protein targets and relatively low levels of lysine acetylation modification, protein enrichment prior to proteomics is sometimes necessary to improve the efficiency and coverage of the analysis ( Jensen et al, 2021 ). An antibody-based enrichment method is one of the most widely used strategies for the characterization of the dynamic acetylome or modifications of a protein of interest ( Inuzuka et al, 2012 ; Lin et al, 2013 ; Miao et al, 2022 ). Here, we describe step-by-step procedures for the identification of acetylated lysine sites of fatty acid synthase (FASN) of fruit fly Drosophila larvae.…”

Section: Introductionmentioning

confidence: 99%

Identification of Acetylation Sites of Fatty Acid Synthase (FASN) by Mass Spectrometry and FASN Activity Assay

Miao,

Bai

2023

BIO-PROTOCOL

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Lysine acetylation is a conserved post-translational modification and a key regulatory mechanism for various cellular processes, including metabolic control, epigenetic regulation, and cellular signaling transduction. Recent advances in mass spectrometry (MS) enable the extensive identification of acetylated lysine residues of histone and non-histone proteins. However, protein enrichment before MS analysis may be necessary to improve the detection of low-abundant proteins or proteins that exhibit low acetylation levels. Fatty acid synthase (FASN), an essential enzyme catalyzing the de novo synthesis of fatty acids, has been found to be acetylated in various species, from fruit flies to humans. Here, we describe a step-by-step process of antibody-based protein enrichment and sample preparation for acetylation identification of endogenous FASN protein by MS-based proteomics analysis. Meanwhile, we provide a protocol for nicotinamide adenine dinucleotide phosphate (NADPH) absorbance assay for FASN activity measurement, which is one of the primary functional readouts of de novo lipogenesis. Key features • A comprehensive protocol for protein immunoprecipitation and sample preparation for acetylation site identification by mass spectrometry. • Step-by-step procedures for measurement of FASN activity of fruit fly larvae using an absorbance assay.

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Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in Drosophila

Cited by 9 publications

References 73 publications

Fat body lipogenic capacity in honey bee workers is affected by age, social role, and dietary protein

Fat body lipogenic capacity in honey bee workers is affected by age, social role, and dietary protein

Role of Fibrinogen-like Protein 1 in Tumor Recurrence Following Hepatectomy

Identification of Acetylation Sites of Fatty Acid Synthase (FASN) by Mass Spectrometry and FASN Activity Assay

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