This scoping review synthesizes the existing research on the use of very low‐calorie diets (VLCDs) in subjects with nonalcoholic fatty liver disease (NAFLD) and end‐stage liver disease (ESLD). 19 studies were included, of which 5 were clinical trials, 11 were cohort studies, 1 was a case‐control study, and 2 were case series totaling 968 subjects. About 17 studies were focused on patients with NAFLD while the two case series described in patients with ESLD on the transplant list or post‐liver transplant. Six studies included subjects managed with VLCDs prior bariatric surgery. Most studies were short term and demonstrated acute improvement of diverse liver biomarkers including liver function tests, indices of hepatosteatosis and reduction in liver size. Adherence rates in these studies were between 69% and 93%. Eight studies did not report any adverse events and four subjects were reported to have discontinued VLCD due to adverse effects in two different studies. Aggregated adverse events were mild. Treatments based on VLCD in subjects with NAFLD seem to be safe and tolerable but can result in mild adverse effects. The findings of this scoping review suggest that the use of VLCD in patients with obesity complicated with NAFLD and potentially in ESLD appear to be effective to induce weight loss and to acutely reduce hepatosteatosis.

The skeletal muscle of type 2 diabetics exhibits mitochondrial dysfunction associated with increased mitochondrial fission. Dynamin-related protein 1 (DRP1) is responsible for mitochondrial division, whereas mitochondrial-endoplasmic reticulum contacts (MERCs) mark mitochondrial sites where fission occurs. Here, we have shown that skeletal muscle-specific DRP1 knock out (KO) mice are partly protected from high fat diet-induced obesity and diabetes, and exhibit increased insulin and glucose tolerance along with lower insulinemia. We also found that KO mice exhibit increased energy expenditure per unit of lean mass. Isolated DRP1-deficient skeletal muscle fibers from KO mice fed high fat diet have reduced respiratory capacity when exposed to ADP and palmitoyl-carnitine, but not when exposed to ADP, pyruvate, and malate. Additionally, the skeletal muscle of KO mice fed normal chow exhibited altered expression of genes associated with MERCs and increased expression of genes linked to ER stress. We observed substantial increases in gene expression of FGF21, a downstream signal of the ER stress response, in KO mice. However, FGF21 plasma concentration in KO mice was not elevated. Additionally, changes in MERC gene expression could potentially alter calcium signaling between the mitochondria and endoplasmic reticulum, changing insulin sensitivity in KO mice. In conclusion, we have shown that skeletal muscle-specific DRP1 KO mice are resistant to high fat diet-induced obesity and diabetes, perhaps due to elevated energy expenditure and differential mitochondrial respiratory adaptations to different substrates. Although FGF21 does not appear to contribute to this effect, it is possible that other ER-stress signals might help explain the observed phenotype in KO mice.