PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes

IF 6.6 2区 医学 Q1 NUTRITION & DIETETICS
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
{"title":"PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes","authors":"Kalliopi Pafili ,&nbsp;Oana-Patricia Zaharia ,&nbsp;Klaus Strassburger ,&nbsp;Birgit Knebel ,&nbsp;Christian Herder ,&nbsp;Maximilian Huttasch ,&nbsp;Yanislava Karusheva ,&nbsp;Stefan Kabisch ,&nbsp;Alexander Strom ,&nbsp;Bettina Nowotny ,&nbsp;Julia Szendroedi ,&nbsp;Michael Roden","doi":"10.1016/j.clnu.2025.02.032","DOIUrl":null,"url":null,"abstract":"<div><h3>Background&amp;aims</h3><div>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 (<em>PNPLA3</em>), which associates with metabolic dysfunction-associated steatotic liver disease, also modulates diet-related metabolic effects.</div></div><div><h3>Methods</h3><div>Participants with type 2 diabetes were randomized to 8-week hypocaloric diets (energy intake: −1,256 kJ/d of, &lt;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 [<sup>2</sup>H]glucose and hyperinsulinemic-normoglycemic clamps, hepatic lipid content (HCL) and body fat volumes by magnetic resonance spectroscopy/imaging before and after intervention.</div></div><div><h3>Results</h3><div>Despite comparable weight loss, HCL decreased more in non-carriers (−65 %) than in G-allele carriers (−36 %) upon HF-RM + C diet (both p &lt; 0.05 vs baseline and between groups), but only among non-carriers (−46 %, p &lt; 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 &gt; 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 &lt; 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 &lt; 0.05 vs baseline).</div></div><div><h3>Conclusions</h3><div>Humans with the <em>PNPLA3</em> G-allele show modified dietary-induced effects on steatotic liver disease in type 2 diabetes despite body weight reduction.</div><div>Registration at <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span>, Identifier number: NCT01409330.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"48 ","pages":"Pages 6-15"},"PeriodicalIF":6.6000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical nutrition","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0261561425000676","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0

Abstract

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.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical nutrition
Clinical nutrition 医学-营养学
CiteScore
14.10
自引率
6.30%
发文量
356
审稿时长
28 days
期刊介绍: Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信