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Published on: November 27, 2019
Time-Restricted Feeding Attenuates Metabolic Dysfunction-Associated Steatohepatitis and Hepatocellular Carcinoma in
Manasi Das1,2, Deepak Kumar1,2, Consuelo Sauceda1,2
1VA San Diego Healthcare System, San Diego, CA 92161, USA.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed the hepatitis B virus and hepatitis C virus as the leading cause of chronic liver disease in most parts of the Western world. MASLD (formerly known as NAFLD) encompasses both simple steatosis and more aggressive metabolic dysfunction-associated steatohepatitis (MASH), which is accompanied by inflammation, fibrosis, and cirrhosis, and ultimately can lead to hepatocellular carcinoma (HCC). There are currently very few approved therapies for MASH. Weight loss strategies such as caloric restriction can ameliorate the harmful metabolic effect of MASH and inhibit HCC; however, it is difficult to implement and maintain in daily life, especially in individuals diagnosed with HCC. In this study, we tested a time-restricted feeding (TRF) nutritional intervention in mouse models of MASH and HCC. We show that TRF abrogated metabolic dysregulation induced by a Western diet without any calorie restriction or weight loss. TRF improved insulin sensitivity and reduced hyperinsulinemia, liver steatosis, inflammation, and fibrosis. Importantly, TRF inhibited liver tumors in two mouse models of obesity-driven HCC. Our data suggest that TRF is likely to be effective in abrogating MASH and HCC and warrant further studies of time-restricted eating in humans with MASH who are at higher risk of developing HCC.
Insights
Time-restricted feeding (TRF) can improve metabolic dysfunction-associated steatotic liver disease (MASLD) and inhibit liver cancer in mice. This nutritional strategy shows promise for treating metabolic dysfunction-associated steatohepatitis (MASH) and associated hepatocellular carcinoma (HCC).
Area of Science:
- Hepatology
- Metabolic Diseases
- Nutritional Science
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, often progressing to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and hepatocellular carcinoma (HCC).
- Current therapeutic options for MASH and HCC are limited, with lifestyle interventions like caloric restriction being challenging for long-term adherence.
Purpose of the Study:
- To investigate the efficacy of time-restricted feeding (TRF) as a nutritional intervention for MASH and HCC in preclinical models.
- To determine if TRF can mitigate metabolic dysregulation and liver pathology without requiring weight loss or calorie restriction.
Main Methods:
- Utilized mouse models of diet-induced MASH and obesity-driven HCC.
- Administered a time-restricted feeding (TRF) regimen.
- Assessed metabolic parameters, liver steatosis, inflammation, fibrosis, and tumor development.
Main Results:
- TRF effectively abrogated diet-induced metabolic dysregulation, improving insulin sensitivity and reducing hyperinsulinemia.
- The intervention ameliorated liver steatosis, inflammation, and fibrosis associated with MASH.
- TRF significantly inhibited liver tumor formation in two distinct models of HCC.
Conclusions:
- Time-restricted feeding demonstrates significant therapeutic potential for both MASH and associated HCC in preclinical studies.
- TRF offers a promising non-caloric restriction-based strategy for managing MASLD progression and preventing HCC.
- Further clinical investigation of time-restricted eating in human patients with MASH and at high risk for HCC is warranted.
