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- Bui, Anh T., et al.
(författare)
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Reduced metabolic flexibility is a predictor of weight gain among liver transplant recipients
- 2023
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Ingår i: Liver transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1527-6465 .- 1527-6473.
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (& beta;-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (& beta;-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (& beta;-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.
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| 2. |
- Siddiqui, Mohammad S., et al.
(författare)
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Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease
- 2022
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Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 42:6, s. 1401-1409
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). Methods Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). Results The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. Conclusion Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.
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| 3. |
- Siddiqui, Mohammad Shadab, et al.
(författare)
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Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients
- 2023
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Ingår i: Liver transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1527-6465 .- 1527-6473. ; 29:9, s. 979-986
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Tidskriftsartikel (refereegranskat)abstract
- NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor & alpha;/& gamma; agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter & GE;264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3 & PLUSMN;10.5% at baseline to 8.1 & PLUSMN;7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.
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