PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes
BACKGROUND&AIMS: Lifestyle-induced weight reduction remains crucial for managing type 2 diabetes and steatotic liver disease, but its effectiveness varies. We postulated that the G allele in the rs738409 single nucleotide polymorphism within patatin-like phospholipase domain-containing protein 3...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
6 March 2025
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| In: |
Clinical nutrition
Year: 2025, Jahrgang: 48, Pages: 6-15 |
| ISSN: | 1532-1983 |
| DOI: | 10.1016/j.clnu.2025.02.032 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.clnu.2025.02.032
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| Verfasserangaben: | Kalliopi Pafili, Oana-Patricia Zaharia, Klaus Strassburger, Birgit Knebel, Christian Herder, Maximilian Huttasch, Yanislava Karusheva, Stefan Kabisch, Alexander Strom, Bettina Nowotny, Julia Szendroedi, Michael Roden |
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| 245 | 1 | 0 | |a PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes |c Kalliopi Pafili, Oana-Patricia Zaharia, Klaus Strassburger, Birgit Knebel, Christian Herder, Maximilian Huttasch, Yanislava Karusheva, Stefan Kabisch, Alexander Strom, Bettina Nowotny, Julia Szendroedi, Michael Roden |
| 264 | 1 | |c 6 March 2025 | |
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| 520 | |a BACKGROUND&AIMS: Lifestyle-induced weight reduction remains crucial for managing type 2 diabetes and steatotic liver disease, but its effectiveness varies. We postulated that the G allele in the rs738409 single nucleotide polymorphism within patatin-like phospholipase domain-containing protein 3 (PNPLA3), which associates with metabolic dysfunction-associated steatotic liver disease, also modulates diet-related metabolic effects. - METHODS: Participants with type 2 diabetes were randomized to 8-week hypocaloric diets (energy intake: -1,256 kJ/d of, <30 kcal% fat): high in cereal fiber and coffee excluding red meat (HF-RM + C; n = 16), or low in cereal fiber, devoid of coffee, but high in red meat (LF + RM-C; n = 15). Whole-body insulin sensitivity (M value) was assessed using [2H]glucose and hyperinsulinemic-normoglycemic clamps, hepatic lipid content (HCL) and body fat volumes by magnetic resonance spectroscopy/imaging before and after intervention. - RESULTS: Despite comparable weight loss, HCL decreased more in non-carriers (-65 %) than in G-allele carriers (-36 %) upon HF-RM + C diet (both p < 0.05 vs baseline and between groups), but only among non-carriers (-46 %, p < 0.05 vs baseline) upon LF + RM-C. Upon HF-RM + C diet, increase in insulin sensitivity was not different between carriers (+27 % p = 0.051 from baseline) and non-carriers (+21 %, p = 0.032 from baseline), p > 0.05 for between-group comparison. Upon LF + RM-C diet, both groups equally improved their whole-body insulin sensitivity (+42 % for non-carriers and +37 % for carriers, p < 0.05 vs baseline). Upon HF-RM + C diet, non-carriers decreased circulating interleukin-18 from baseline by -31 %, whereas, upon LF + RM-C diet, non-carriers decreased circulating anti-inflammatory interleukin-1 receptor antagonist levels by 14 % (both p < 0.05 vs baseline). - CONCLUSIONS: Humans with the PNPLA3 G-allele show modified dietary-induced effects on steatotic liver disease in type 2 diabetes despite body weight reduction. Registration at Clinicaltrials.gov, Identifier number: NCT01409330. | ||
| 650 | 4 | |a Aged | |
| 650 | 4 | |a Alleles | |
| 650 | 4 | |a Caloric restriction | |
| 650 | 4 | |a Caloric Restriction | |
| 650 | 4 | |a Diabetes mellitus | |
| 650 | 4 | |a Diabetes Mellitus, Type 2 | |
| 650 | 4 | |a Diet, Reducing | |
| 650 | 4 | |a Dietary Fiber | |
| 650 | 4 | |a Female | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Insulin resistance | |
| 650 | 4 | |a Insulin Resistance | |
| 650 | 4 | |a Lipase | |
| 650 | 4 | |a Lipid Metabolism | |
| 650 | 4 | |a Liver | |
| 650 | 4 | |a Macronutrients | |
| 650 | 4 | |a Male | |
| 650 | 4 | |a Membrane Proteins | |
| 650 | 4 | |a Metabolic dysfunction-associated steatotic liver disease | |
| 650 | 4 | |a Middle Aged | |
| 650 | 4 | |a Obesity | |
| 650 | 4 | |a Phospholipases A2, Calcium-Independent | |
| 650 | 4 | |a Polymorphism, Single Nucleotide | |
| 650 | 4 | |a Weight Loss | |
| 700 | 1 | |a Zaharia, Oana-Patricia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Strassburger, Klaus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Knebel, Birgit |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herder, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Huttasch, Maximilian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Karusheva, Yanislava |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kabisch, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Strom, Alexander |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nowotny, Bettina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Szendrödi, Julia |e VerfasserIn |0 (DE-588)1226436463 |0 (DE-627)1747448249 |4 aut | |
| 700 | 1 | |a Roden, Michael |e VerfasserIn |4 aut | |
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