Ketoacidosis Starvation

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Hepatocellular Carcinoma Redirects To Ketolysis For Progression Under Nutrition Deprivation Stress

Cancer cells are known for their capacity to rewire metabolic pathways to support survival and proliferation under various stress conditions. Ketone bodies, though produced in the liver, are not consumed in normal adult liver cells. We find here that ketone catabolism or ketolysis is re-activated in hepatocellular carcinoma (HCC) cells under nutrition deprivation conditions. Mechanistically, 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting ketolytic enzyme whose expression is suppressed in normal adult liver tissues, is re-induced by serum starvation-triggered mTORC2-AKT-SP1 signaling in HCC cells. Moreover, we observe that enhanced ketolysis in HCC is critical for repression of AMPK activation and protects HCC cells from excessive autophagy, thereby enhancing tumor growth. Importantly, analysis of clinical HCC samples reveals that increased OXCT1 expression predicts higher patient mortality. Taken together, we uncover here a novel metabolic adaptation by which nutrition-deprived HCC cells employ ketone bodies for energy supply and cancer progression. Compared with their normal counterparts, cancer cells are metabolically reprogrammed in order to obtain sufficient energy or add Continue reading >>

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Popular Questions

  1. William Keating

    For commercial aircraft: mountain wave, changing winds, slow aircraft or pilot response to airspeed fluctuations. It is not necessarily even a serious inspection depending on the amount the limit is exceeded. Exceeding airframe speed limits is rarely the real cause of aircraft incidents.

  2. Ronald Sanders

    I just add one scenario: cruising at maximum operating mach number you get a horizontal windshear and you will momentarily exceed that limit. This is common enough to prompt us to set overspeed warning at a few knots above mmo. Traversing the jet steam or entering strong frontal systems can lead to significant headwind changes.

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  3. Jason Yap

    Recover from a stall or spin
    Stall or spin will not induct an aircraft to exceed speed limit. With a suitable height, the aircraft is available to spin for a very long time until you intend to recover. In example, you can start to recover above 5000ft so that you will have more time and distance to the ground. In the recovery process, you have to pitch your nose down while spinning adjacent to all and singular three axis, your airspeed will not increase. However, in that point you wish to recover from a stall, an inadequate recovery is taking a risk to exceed the never exceed speed (Vne).
    Spiral dive
    In a spiral dive without adjusting the throttle, the aircraft is pointed into the relative wind, aircraft nose is pitching down and it is in a descending turn. This situation is the phrase where things get complicated. The aircraft will get tighter turns as the nose is dropping lower, speed of the aircraft will go higher. If this situation prolonged, you will exceed the never exceed speed (Vne) and you will have structural damage to your aircraft. You might end up having a land or sea impact if you have insufficient time or height to recover. When you are conducting a coordinated turn, if you don't look out the window or use the instruments, you will not figure out that you are turning, descending or accelerating and that may lead to a spiral dive.

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