Dataset Information

The role of ANKRD9 in mouse jejunal enteroids.

ABSTRACT: The absorption of dietary fats represents one of the most energy-intensive processes involved in nutrient uptake. Processes such as fatty acid activation, triglyceride synthesis, and the trafficking of chylomicrons through the secretory pathway require ATP. The mechanism by which enterocytes manage the increased ATP demand following fat absorption remains unclear. Ankyrin Repeat Domain 9 (ANKRD9) has been identified as a fat responsive protein. Our research revealed that the inactivation of Ankrd9 results in a significant decrease in ATP levels within enterocytes, without affecting mitochondrial function or glycolysis, and leads to increased lipid accumulation, thereby reducing body fat mass. These findings suggest that ANKRD9 plays a crucial role in the regulation of ATP and fat processing. To further elucidate the function of ANKRD9 in enterocytes, we conducted proteomic analyses of jejunal differentiated enteroids derived from wild-type (Ankrd9+/+) and Ankrd9 knockout (Ankrd9-/-) mice.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Jejunum

SUBMITTER: chanhyun na

LAB HEAD: Chan-Hyun Na

PROVIDER: PXD073421 | Pride | 2026-03-12

REPOSITORIES: Pride

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			Action	DRS
	210713_LutsenkoS_AZ_TMT10_BioRep_NormUnmod_sn5_Iso25_.msf	Msf
	210713_LutsenkoS_AZ_TMT10_BioRep_NormUnmod_sn5_Iso25_.msfView	Msf
	210713_LutsenkoS_AZ_TMT10_BioRep_NormUnmod_sn5_Iso25_.pdResult	Other
	210713_LutsenkoS_AZ_TMT10_BioRep_NormUnmod_sn5_Iso25_.pdResultView	Other
	TB-CS-LE-210713_LutsenkoS_AZ_TMT10_10.raw	Raw

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Project description:Despite the crucial function of the small intestine for nutrient uptake our understanding of the molecular events underlying the digestive function is very rudimentary. For example, it has only recently become evident that not all absorbed triacylglycerol (TAG) is immediately secreted in the form of chylomicrons (CM) by enterocytes. Instead, especially after high-fat challenges, parts of the re-synthesized TAG can be packaged into cytosolic lipid droplets (CLD) for transient storage in the endothelial layer of the small intestine. The reasons for this intermediate storage of TAGs are currently not completely understood. Several mechanisms, including alleviating lipotoxicity to enterocytes, limits in the rate of CM assembly or smoothening of the post-prandial peaks of blood hypertriglyceridemia have been suggested to explain this intermediate storage of TAG in CLD. Interestingly, rather than being evenly distributed across the small intestine, the proximal jejunum exhibits the highest TAG storage and CM secretion. Once stored in CLD, lipids are either remobilized in the inter-prandial phase or by various stimuli, e.g. a sequential meal containing either lipids or glucose. After remobilization, a triglyceride peak can be observed in the form of plasma CM well before lipids from the second meal have been digested in the intestinal lumen. To synthesize CM with lipids from CLD, CLD TAG have to be hydrolyzed to be transported across the ER membrane which can either be achieved by cytoplasmic TAG lipolysis or lipophagy. We hypothesize that correlating enzymatic activities of hydrolases with the reported distribution of TAG storage and chylomicron secretion in different sections of the small intestine is a promising strategy to pinpoint the key players in TAG remobilization. To rank hydrolases based on their relative activity in the different sections of the small intestine we have harnessed a serine hydrolase specific activity-based labeling strategy to label active hydrolases in freshly harvested enterocytes. Enrichment of activity labeled enzymes over control samples and abundance of enriched hydrolases from individual small intestine sections was analyzed using quantitative proteomics, resulting in a ranking of the most active hydrolases in 11 fractions of murine small intestine. Moreover, several clusters of enzymes showing similar activity distribution along the small intestine were identified.

Project description:Progressive supranuclear palsy (PSP) is a neurodegenerative disorder clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism, and cognitive decline caused by degeneration in specific areas of the brain including globus pallidus (GP), substantia nigra, and subthalamic nucleus. However, the pathogenetic mechanism of PSP remains unclear to date. Unbiased global proteome analysis of patients’ brain samples is an important step toward understanding PSP pathogenesis, as proteins serve as workhorses and building blocks of the cell. In this study, we conducted unbiased mass spectrometry-based global proteome analysis of GP samples from 15 PSP patients, 15 Parkinson disease (PD) patients, and 15 healthy control (HC) individuals. To analyze 45 samples, we conducted 5 batches of 11-plex isobaric tandem mass tag (TMT)-based multiplexing experiments, identifying 10,231 proteins. The gene set enrichment analysis results showed that the PD pathway was the most highly enriched, followed by pathways for oxidative phosphorylation, Alzheimer disease, Huntington disease, and non-alcoholic fatty liver disease (NAFLD) when PSP was compared to HC or PD. Most of the proteins enriched in the gene set enrichment analysis were mitochondrial proteins such as cytochrome c oxidase, NADH dehydrogenase, acyl carrier protein, succinate dehydrogenase, ADP/ATP translocase, cytochrome b-c1 complex, and/or ATP synthase. Strikingly, all of the enriched mitochondrial proteins in the PD pathway were downregulated in PSP compared to both HC and PD. The subsequent Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) protein-protein interaction (PPI) analysis and the weighted gene co-expression network analysis (WGCNA) further supported that the mitochondrial proteins were the most highly enriched in PSP. This is the first global proteome analysis of human GP from PSP patients, and this study paves the way to understanding the pathogenesis mechanism of PSP.

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The role of ANKRD9 in mouse jejunal enteroids.

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