Long-term effects of increased protein intake after weight loss on intrahepatic lipid content and implications for insulin sensitivity: a PREVIEW study

Drummen, Mathijs; Dorenbos, Elke; Vreugdenhil, Anita; Raben, Anne; Fogelholm, Mikael; Westerterp-Plantenga, Margriet S.; Adam, Tanja C.

doi:10.1152/ajpendo.00162.2018

Cited by 16 publications

(15 citation statements)

References 49 publications

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“…However, the study was conducted in healthy subjects with BMI of 24 kg/m 2 and IHL below 0.4% at baseline. Similarly, Drummen et al observed a significant decrease in IHL in obese participants after 8 weeks of hypocaloric HP diet (35‐40 E% protein) and 20 weeks of hypocaloric HP diet 32 . Important result of our study is that we demonstrated the strong reduction in liver fat already after a short‐term (3‐weeks) HP diet.…”

Section: Discussionsupporting

confidence: 83%

High‐protein diet more effectively reduces hepatic fat than low‐protein diet despite lower autophagy and FGF21 levels

Markova

Seebeck

et al. 2020

Liver International

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Background and aims Non‐alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low‐ (LP) or high‐protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. Methods 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500‐1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. Results IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA‐seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β‐oxidation genes did not increase in the HP group. Conclusions HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.

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Section: Discussionsupporting

confidence: 83%

High‐protein diet more effectively reduces hepatic fat than low‐protein diet despite lower autophagy and FGF21 levels

Markova

Seebeck

et al. 2020

Liver International

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“…For example, plant protein but not animal protein has been reported to reduce mortality risk in people with diabetes (81) . The feasibility of improving dietary protein as an approach to NAFLD is further supported by the recent report that an increase in daily protein intake to 25 % by weight was sufficient to reduce intrahepatic lipid accumulation in people with diabetes following a weight-reduction diet (80) . This beneficial effect on fat storage in the liver was observed during a 2-year follow-up period of weight maintenance and was independent of BMI.…”

Section: Resultsmentioning

confidence: 97%

“…Two population-based studies have explored the effects of increasing dietary protein after weight loss in people with diabetes (79,78) . In the PREVIEW study, the prospective association between increased plant protein intake and improvement in diabetes indicators and fatty liver was reported to be independent of BMI (78,80) . In a secondary analysis of data from the randomised controlled DIOGenes trial, which investigated dietary protein composition and glycaemic index on weight loss maintenance and cardiometabolic risk factors in obesity, plant protein offered the greatest health benefits, while a higher plant protein intake from non-cereal products instead of cereal products (matched by a decrease in other sources of protein intake) benefited by body weight maintenance and blood pressure (79) .…”

Section: Associative Evidence Between Low Dietary Protein and Fatty Lmentioning

confidence: 99%

Dietary protein insufficiency: an important consideration in fatty liver disease?

et al. 2019

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Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.

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“…Low intake of fibres, vitamins, and mineral nutrients support NAFLD progression [ 143 ], whereas dietary habits rich in fruits and vegetables have antioxidant, anti-inflammatory effects, and can improve IR [ 144 ]. Protein diets in subjects with T2DM and NAFLD promotes loss of hepatic fat associated with better IR and decreased hepatic cytolytic profile [ 145 ], and can improve the glycated haemoglobin A1c (HbA1c) levels [ 146 ]. Contrary, others showed that a high protein diet may have negative effects on insulin sensitivity, and its beneficial effects are linked to the amount and quality of the products [ 147 ].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD)

Tănase

Gosav

Costea

et al. 2020

Journal of Diabetes Research

275

180

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Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) remain as one of the most global problematic metabolic diseases with rapidly increasing prevalence and incidence. Epidemiological studies noted that T2DM patients have by two-fold increase to develop NAFLD, and vice versa. This complex and intricate association is supported and mediated by insulin resistance (IR). In this review, we discuss the NAFLD immunopathogenesis, connection with IR and T2DM, the role of screening and noninvasive tools, and mostly the impact of the current antidiabetic drugs on steatosis liver and new potential therapeutic targets.

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Long-term effects of increased protein intake after weight loss on intrahepatic lipid content and implications for insulin sensitivity: a PREVIEW study

Abstract: A 2-year medium- to high-protein energy restricted diet reduced IHL and VAT. Independently of changes in BMI, IHL was inversely related to insulin sensitivity.

Cited by 16 publications

References 49 publications

High‐protein diet more effectively reduces hepatic fat than low‐protein diet despite lower autophagy and FGF21 levels

High‐protein diet more effectively reduces hepatic fat than low‐protein diet despite lower autophagy and FGF21 levels

Dietary protein insufficiency: an important consideration in fatty liver disease?

The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD)

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