Effect of Weight Loss on Liver Free Fatty Acid Uptake and Hepatic Insulin Resistance

Viljanen, Antti; Iozzo, Patricia; Borra, Ronald; Kankaanpää, M.; Karmi, Anna; Lautamäki, Riikka; Järvisalo, Mikko J.; Parkkola, Riitta; Rönnemaa, Tapani; Guiducci, Letizia; Lehtimäki, Terho; Raitakari, Olli T.; Mari, Andrea; Nuutila, Pirjo

doi:10.1210/jc.2008-1689

Cited by 107 publications

(91 citation statements)

References 31 publications

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“…The achieved weight loss led to a reduction in ALT and triglyceride levels at the end of the study comparable to related studies showing a parallel reduction in triglyceride uptake and liver-storage after a 6 week period of calorie restriction [35]. These results suggest a reduction in liver fat content in our patients as well.…”

Section: Discussionsupporting

confidence: 88%

Fetuin-A as a Possible Marker of Nonalcoholic Fatty Liver Disease in Patients with Non-Surgical Weight Loss

Jb¹,

Lehnhoff²,

Roeder³

et al. 2017

J Obes Weight Loss Ther

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Objective: Overweight and obesity are ranked as the fifth leading cause for global deaths and significantly contribute to nonalcoholic fatty liver disease (NAFLD), a common comorbidity finally leading to end-stage liver disease. The diagnostic tool for confirming NAFLD is liver biopsy, an invasive procedure known to cause complications. Results from transient elastography are not reliable in obese patients. Therefore, alternative diagnostic approaches are necessary. One putative biomarker is fetuin-A, also known as α 2 -Heremans-Schmid Glycoprotein (AHSG), which has been proposed for the diagnosis of NAFLD. We therefore aimed to examine the role of fetuin-A in severely obese patients and its value in predicting NAFLD.Methods: 62 obese patients with a body mass index of at least 30 kg/m² undergoing a medically supervised weight loss program were analysed at time points T0 (before weight loss), T1 (after non-surgical weight loss within 12 weeks), and T2 (after 52 weeks). Anthropometrical parameters, laboratory values for NAFLD, fetuin-A, "Fatty Liver-index" (FLI), and NASH-Score were determined.Results: 38 out of 62 patients completed the program. These patients showed a significant decrease in BMI (T0: 41.5 ± 7.1 kg/m²; T2: 33.5 ± 7.0 kg/m²; p<0.001 each). While markers of NAFLD improved from T0 to T2, no significant change was observed in fetuin-A (p=0.36). FLI and NASH-Score significantly improved over time (p ≤ 0.001; p=0.03). Both scores failed to show a correlation with fetuin-A at baseline or during the program. Conclusion:Fetuin-A does not appear to be suitable for diagnosis and follow-up of NAFLD in patients with severe obesity.

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Section: Discussionsupporting

confidence: 88%

Fetuin-A as a Possible Marker of Nonalcoholic Fatty Liver Disease in Patients with Non-Surgical Weight Loss

Jb¹,

Lehnhoff²,

Roeder³

et al. 2017

J Obes Weight Loss Ther

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“…Diet only interventions We identified 11 eligible study groups including 322 participants (approximately 65% women, 20 controls) prescribing dietary change: six using low-to-moderate fat/moderate-to-high carbohydrate energy restricted diets [25][26][27][28][29][30], one of which also specifically restricted iron intake [27]; three groups were given low carbohydrate ketogenic diets [26,31,32]; and two high protein diets [30,33]. Two studies employed biopsy [27,31], but only one at follow-up [31], the other used ALT and AST at follow-up [27]; three used 1 H-MRS [26,28,30], two used CT [25,32], three studies relied on ALT and AST [29,33].…”

Section: Study Findingsmentioning

confidence: 99%

“…Two studies employed biopsy [27,31], but only one at follow-up [31], the other used ALT and AST at follow-up [27]; three used 1 H-MRS [26,28,30], two used CT [25,32], three studies relied on ALT and AST [29,33]. Only two studies had a control group [25,27]; in one the control group were those with low adherence to the protocol [25].…”

Section: Study Findingsmentioning

confidence: 99%

Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: A systematic review

Thoma

Day

Trenell

2012

Journal of Hepatology

458

334

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Non-alcoholic fatty liver disease is a serious and growing clinical problem. Despite lifestyle modification, i.e. diet and physical activity, being the recommended therapy, there are currently no systematic evaluations of its efficacy. This review applies a systematic approach to evaluating lifestyle modifications studied to date. Medline (Pubmed), Scopus, and the Cochrane Controlled Trials Register were searched for studies and study groups assessing the effect of diet, physical activity, and/or exercise modification in adult populations with non-alcoholic fatty liver disease. The outcome markers of interest were indicators of steatosis, histological evidence of inflammation and fibrosis, and glucose control/insulin sensitivity. We identified 23 studies for inclusion; seven had control groups, but only six were randomised. Eleven groups received diet-only interventions, two exercise-only, and 19 diet and physical activity/exercise. Studies consistently showed reductions in liver fat and/or liver aminotransferase concentration, with the strongest correlation being with weight reduction. Of the 5 studies reporting changes in histopathology, all showed a trend towards reduction in inflammation, in 2 this was statistically significant. Changes in fibrosis were less consistent with only one study showing a significant reduction. The majority of studies also reported improvements in glucose control/insulin sensitivity following intervention. However, study design, definition of disease, assessment methods, and interventions varied considerably across studies. Lifestyle modifications leading to weight reduction and/or increased physical activity consistently reduced liver fat and improved glucose control/insulin sensitivity. Limited data also suggest that lifestyle interventions may hold benefits for histopathology.

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“…44 Whether the hepatic benefit of exercise reflects lower adipose lipolysis and FFA availability and/or a direct effect on hepatic FFA uptake independent of FFA concentration is unclear. In the context of diet-induced weight loss, reductions in liver fat parallel the attenuation of hepatic FFA uptake despite similar basal FFA concentrations, 47 which suggests that the liver may not be a passive bystander with adipose tissue acting as the locus of control. Therefore, it has been suggested that hepatic fatty acid uptake may be regulated, 48 perhaps through altered expression and activity of fatty acid translocase or cluster of differentiation 36 (CD36).…”

Section: Nafld Pathophysiology and The Mechanism Of An Exercise Effectmentioning

confidence: 99%

Fitness versus fatness: Moving beyond weight loss in nonalcoholic fatty liver disease

2010

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The rapid emergence of nonalcoholic fatty liver disease (NAFLD) as a cause of both liverrelated morbidity and mortality and cardiometabolic risk has led to the search for effective lifestyle strategies to reduce liver fat. Lifestyle intervention comprising dietary restriction in conjunction with increased physical activity has shown clear hepatic benefits when weight loss approximating 3%-10% of body weight is achieved. Yet, the poor sustainability of weight loss challenges the current therapeutic focus on body weight and highlights the need for alternative strategies for NAFLD management. Epidemiologic data show an independent relationship between liver fat, physical activity, and fitness, and a growing body of longitudinal research demonstrates that increased physical activity participation per se significantly reduces hepatic steatosis and serum aminotransferases in individuals with NAFLD, independent of weight loss. Mechanistic insights to explain this interaction are outlined, and recommendations for the implementation of lifestyle intervention involving physical activity are discussed. In light of the often poor sustainability of weight loss strategies, and the viability of physical activity therapy, clinicians should assess physical fitness and physical activity habits, educate patients on the benefits of fitness outside of weight loss, and focus on behavior change which promotes physical activity adoption. (HEPATOLOGY 2010;52:370-381)

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Effect of Weight Loss on Liver Free Fatty Acid Uptake and Hepatic Insulin Resistance

Abstract: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.

Cited by 107 publications

References 31 publications

Fetuin-A as a Possible Marker of Nonalcoholic Fatty Liver Disease in Patients with Non-Surgical Weight Loss

Fetuin-A as a Possible Marker of Nonalcoholic Fatty Liver Disease in Patients with Non-Surgical Weight Loss

Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: A systematic review

Fitness versus fatness: Moving beyond weight loss in nonalcoholic fatty liver disease

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