Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.27 (AMPK)
 6,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular long-chain fatty acids' (LCFAs) uptake is a crucial physiological process that regulates cellular energy homeostasis. AMPK has been shown to modulate LCFAs uptake in several kinds of cells, but whether it exerts an impact on intestinal LCFAs uptake is not quite clear. In the current study, we found that AMPK reinforced LCFAs uptake in intestinal epithelial cells (IECs). Moreover, intestinal epithelium-specific AMPK deletion impaired intestinal LCFAs absorption and protected mice from high-fat diet-induced obesity. Mechanistically, we discovered that AMPK deletion reduced the CD36 protein level by upregulating Parkin-mediated polyubiquitination of CD36 in IECs. Furthermore, our results revealed that AMPK affected PARK2 (gene name of Parkin) mRNA stability in a YTHDF2-dependent manner through FTO-dependent demethylation of N6 -methyladenosine (m6 A). Besides, AMPK promoted the translocation of CD36 to the plasma membrane in IECs, but the inhibition of AKT signaling suppressed this effect, which also halted the accelerated fatty acid uptake induced by AMPK. These results suggest that AMPK facilitates the intestinal LCFAs uptake by upregulating CD36 protein abundance and promoting its membrane translocation simultaneously. Such findings shed light on the role of AMPK in the regulation of intestinal LCFAs uptake.
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PMID:AMPK facilitates intestinal long-chain fatty acid uptake by manipulating CD36 expression and translocation. 3204 47

Nearly all diseases in humans, to a certain extent, exhibit sex differences, including differences in the onset, progression, prevention, therapy, and prognosis of diseases. Accumulating evidence shows that macroautophagy/autophagy, as a mechanism for development, differentiation, survival, and homeostasis, is involved in numerous aspects of sex differences in diseases such as cancer, neurodegeneration, and cardiovascular diseases. Advances in our knowledge regarding sex differences in autophagy-mediated diseases have enabled an understanding of their roles in human diseases, although the underlying molecular mechanisms of sex differences in autophagy remain largely unexplored. In this review, we discuss current advances in our insight into the biology of sex differences in autophagy and disease, information that will facilitate precision medicine.Abbreviations: AD: Azheimer disease; AMBRA1: autophagy and beclin 1 regulator 1; APP: amyloid beta precursor protein; AR: androgen receptor; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP6AP2: ATPase H+ transporting accessory protein 2; BCL2L1: BCL2 like 1; BECN1: beclin 1; CTSD: cathepsin D; CYP19A1: cytochrome P450 family 19 subfamily A member 1; DSD: disorders of sex development; eALDI: enhancer alternate long-distance initiator; ESR1: estrogen receptor 1; ESR2: estrogen receptor 2; FYCO1: FYVE and coiled-coil domain autophagy adaptor 1; GABARAP: GABA type A receptor-associated protein; GLA: galactosidase alpha; GTEx: genotype-tissue expression; HDAC6: histone deacetylase 6; I-R: ischemia-reperfusion; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; m6A: N6-methyladenosine; MYBL2: MYB proto-oncogene like 2; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PSEN1: presenilin 1; PSEN2: presenilin 2; RAB9A, RAB9A: member RAS oncogene family; RAB9B, RAB9B: member RAS oncogene family; RAB40AL: RAB40A like; SF1: splicing factor 1; SOX9: SRY-box transcription factor 9; SRY: sex determining region Y; TFEB: transcription factor EB; ULK1: unc-51 like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; VDAC2: voltage dependent anion channel 2; WDR45: WD repeat domain 45; XPDS: X-linked parkinsonism and spasticity; YTHDF2: YTH N6-methyladenosine RNA binding protein 2.
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PMID:Sex differences in autophagy-mediated diseases: toward precision medicine. 3226 24