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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All organisms have devised strategies to counteract energy depletion and promote fitness for survival. We show here that cellular energy depletion puts into play a surprising strategy that leads to absorption of exogenous fuel for energy repletion. The energy-depletion-sensing kinase AMPK binds, phosphorylates, and activates the transcriptional coactivator SRC-2, which in a liver-specific manner promotes absorption of dietary fat from the gut. Hepatocyte-specific deletion of SRC-2 results in intestinal fat malabsorption and attenuated entry of fat into the blood stream. This defect can be attributed to AMPK- and SRC-2-mediated transcriptional regulation of hepatic bile acid (BA) secretion into the gut, as it can be completely rescued by replenishing intestinal BA or by genetically restoring the levels of hepatic bile salt export pump (BSEP). Our results position the hepatic AMPK-SRC-2 axis as an energy rheostat, which upon cellular energy depletion resets whole-body energy by promoting absorption of dietary fuel.
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PMID:Cellular energy depletion resets whole-body energy by promoting coactivator-mediated dietary fuel absorption. 2119 40

The collateral effects of obesity/metabolic syndrome include inflammation and renal function decline. As renal disease in obesity can occur independently of hypertension and diabetes, other yet undefined causal pathological pathways must be present. Our study elucidate novel pathological pathways of metabolic renal injury through LDL-induced lipotoxicity and metainflammation. Our in vitro and in vivo analysis revealed a direct lipotoxic effect of metabolic overloading on tubular renal cells through a multifaceted mechanism that includes intralysosomal lipid amassing, lysosomal dysfunction, oxidative stress, and tubular dysfunction. The combination of these endogenous metabolic injuries culminated in the activation of the innate immune NLRP3 inflammasome complex. By inhibiting the sirtuin-1/LKB1/AMPK pathway, NLRP3 inflammasome dampened lipid breakdown, thereby worsening the LDL-induced intratubular phospholipid accumulation. Consequently, the presence of NLRP3 exacerbated tubular oxidative stress, mitochondrial damage and malabsorption during overnutrition. Altogether, our data demonstrate a causal link between LDL and tubular damage and the creation of a vicious cycle of excessive nutrients-NLRP3 activation-catabolism inhibition during metabolic kidney injury. Hence, this study strongly highlights the importance of renal epithelium in lipid handling and recognizes the role of NLRP3 as a central hub in metainflammation and immunometabolism in parenchymal non-immune cells.
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PMID:Metabolic injury-induced NLRP3 inflammasome activation dampens phospholipid degradation. 2858 89

The intestine integrates the function of digestion, absorption, and barrier, which is easily damaged by the external factors upon ageing. The intestinal stem cells (ISCs) exist at the intestinal crypt base and play an indispensable role in intestinal homeostasis and regeneration. The intestine ageing contributes to malabsorption and other associated illnesses, which were considered to be related to ISCs. Here, we summarize the current research progress of mammalian ISCs ageing and pay more attention to the central regulatory role of the mTORC1 signaling pathway in regulating mammalian ISCs ageing, and its related AMPK, FOXO, Wnt signaling pathways. Furthermore, we also discuss the interventions aimed at mTORC1 and its associated signaling pathways, which may provide potential strategies for rejuvenating aged ISCs and the therapy of age-related intestinal diseases. Graphical abstract Many signaling pathways are altered in the ageing ISCs, thereby inducing the decrease of ISC self-renewal, differentiation, and regeneration, an increasing of oxidative stress may contribute to damage to the ISCs. Interventions such as calorie restriction, fasting and so on can effectively alleviate these adverse effects.
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PMID:Signaling Network Centered on mTORC1 Dominates Mammalian Intestinal Stem Cell Ageing. 3320 40