ArticleEMBO molecular medicine2021
Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 29 citations in OpenAlex.
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- Platelet-derived lipids promote insulin secretion of pancreatic β cells.EMBO molecular medicine · 2023Article
- From worms to humans: Understanding intestinal lipid metabolism via model organisms.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Review
- Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel.Lipids in health and disease · 2023Article
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
- When fat meets the gut-focus on intestinal lipid handling in metabolic health and disease.EMBO molecular medicine · 2022Review
- Genetic variants associated with circulating liver injury markers in Mexican Americans, a population at risk for non-alcoholic fatty liver disease.Frontiers in genetics · 2022Article
- A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism.Life science alliance · 2021Article
- Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.EMBO molecular medicine · 2021Article
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipids are the most energy-dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron-mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high-fat diet-induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity.
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