What is the mechanism of inhibition of lipogenesis in the liver after several weeks on a ketogenic diet (KD)?

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From the Research

After several weeks on a ketogenic diet, lipogenesis in the liver is inhibited primarily due to hormonal and metabolic adaptations, as evidenced by the most recent study in 2022 1. The ketogenic diet dramatically reduces carbohydrate intake while increasing fat consumption, which lowers insulin levels in the bloodstream.

  • Insulin normally promotes lipogenesis, so its reduction directly decreases the liver's fat-producing activity.
  • Additionally, the diet increases glucagon levels, which opposes insulin's effects and further suppresses lipogenesis. The liver also undergoes enzymatic changes, with decreased activity of lipogenic enzymes like acetyl-CoA carboxylase and fatty acid synthase, while simultaneously upregulating enzymes involved in fatty acid oxidation, as shown in a study from 2022 1.
  • The transcription factor SREBP-1c, which normally activates genes for fat synthesis, becomes less active during ketosis. These adaptations collectively shift the liver's metabolism away from fat production and toward fat utilization, helping the body maintain energy homeostasis during carbohydrate restriction and promoting the use of ketone bodies as an alternative fuel source. However, it is essential to consider the potential long-term effects of a ketogenic diet, as a study from 2024 2 suggests that it may lead to hyperlipidemia, liver dysfunction, and glucose intolerance. Despite this, the most recent and highest-quality study from 2022 1 supports the use of a ketogenic diet to treat non-alcoholic fatty liver disease (NAFLD) due to its anti-steatogenic and insulin-sensitizing effects in the liver.

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