Abstract
CONTEXT: Liver fat is reduced within days after a low-carbohydrate diet substituted with fat to maintain isocaloric conditions.
OBJECTIVE: Investigate the effect of matched carbohydrate restriction during isocaloric and hypocaloric conditions on liver fat and postprandial glucose and lipid metabolism.
METHODS: Crossover randomized clinical trial at a research unit. Participants included 15 people with overweight/obesity (body mass index [BMI] 32.5 [31-34] kg/m2, median [IQR]). There were 3 dietary interventions: (1) 2 days of isocaloric control diet (CON), (2) 2 days of CON followed by 2 days of carbohydrate restriction (∼60 g/day) during very-low-calorie conditions (VLCDs), and (3) 2 days of CON followed by 2 days of isocaloric conditions with low carbohydrate (∼60 g/day), high-fat (LCHF) diet. Liver fat was measured using 1H-magnetic resonance spectroscopy.
RESULTS: Liver fat was -16% (-34; 4) (median [IQR]) after LCHF relative to after CON (P = .020), but did not differ between VLCD and CON. Fasting plasma concentrations of triacylglycerol, glucose, and insulin were lower after both LCHF and VLCD than after CON. However, postprandial plasma glucose concentrations were higher and insulinogenic index lower after both LCHF and VLCD.
CONCLUSION: Two days of LCHF led to lower liver fat, which was not observed after VLCD. This demonstrates the dynamic regulation of liver fat and the beneficial role of substituting carbohydrates with fat to maintain energy provision. Both LCHF and VLCD had positive effects on fasting parameters for glucose metabolism; however, both diets impaired early β-cell response resulting in deterioration in glucose handling during the meal test.
| Original language | English |
|---|---|
| Journal | The Journal of clinical endocrinology and metabolism |
| Volume | 111 |
| Issue number | 2 |
| Pages (from-to) | 449-460 |
| Number of pages | 12 |
| ISSN | 0021-972X |
| DOIs | |
| Publication status | Published - 21 Jan 2026 |
Keywords
- Adult
- Blood Glucose/metabolism
- Caloric Restriction/methods
- Cross-Over Studies
- Diet, Carbohydrate-Restricted/methods
- Female
- Glucose/metabolism
- Humans
- Lipid Metabolism/physiology
- Liver/metabolism
- Male
- Middle Aged
- Obesity/metabolism
- Overweight/metabolism
- Postprandial Period
- low-carbohydrate
- lipid metabolism
- mixed meal test
- MASLD (metabolic dysfunction–associated steatotic liver disease)
- glucose metabolism
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