Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars

Abstract

Debate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males. RESEARCH DESIGN AND METHODSSixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period. The metabolic effects of the respective diets on IHTAG content, hepatic DNL, and wholebody metabolism were investigated using imaging techniques and metabolic substrates labeled with stable-isotope tracers. RESULTSConsumption of the SFA diet significantly increased IHTAG by mean 6 SEM 39.0 6 10.0%, while after the SUGAR diet IHTAG was virtually unchanged. Consumption of the SFA diet induced an exaggerated postprandial glucose and insulin response to a standardized test meal compared with SUGAR. Although whole-body fat oxidation, lipolysis, and DNL were similar following the two diets, consumption of the SUGAR diet resulted in significant (P < 0.05) decreases in plasma total, HDL, and non-HDL cholesterol and fasting b-hydroxybutyrate plasma concentrations. CONCLUSIONSConsumption of an SFA diet had a potent effect, increasing IHTAG together with exaggerating postprandial glycemia. The SUGAR diet did not influence IHTAG and induced minor metabolic changes. Our findings indicate that a diet enriched in SFA is more harmful to metabolic health than a diet enriched in free sugars.Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver-related conditions, ranging from steatosis (characterized by an accumulation of intrahepatic triacylglycerol [IHTAG]) to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, and is the most prevalent liver disease worldwide (1). There appears to exist a bidirectional relationship between NAFLD and metabolic disease; the presence

Mitochondrial Dysfunction is a Key Pathway that Links Saturated Fat Intake to the Development and Progression of NAFLD

“…In line with this, a very recent study showed that also an isocaloric diet enriched in SFA increased liver fat and postprandial glycaemia, whereas an isocaloric diet high in sugar had no effect on liver fat and induced only minor metabolic changes. [ 18 ]…”

“…Interestingly, while the present article was under review, a study was published which showed that humans given an isocaloric diet high in SFA also increased their liver fat and postprandial glycaemia, whereas a isocaloric diet high in sugar had no effect on liver fat and induced only minor metabolic changes. [ 18 ] Studies are now needed to compare the effect of an isocaloric diet high in SFA with an isocaloric diet high in PUFA on liver fat, and with a stronger focus toward underlying mechanisms. Of note, studies should also look into the possible differential effects of SFA originating from dairy sources as opposed to SFA coming from meat.…”

Regulating metabolic inflammation by nutritional modulation

“…Indeed, Hodson's team recently demonstrated that feeding SFAs increased hepatic lipogenesis to a greater extent than simple sugars did. 111 When the data are taken together, the belief that dietary composition plays a significant role in metabolic disease development is supported by strong clinical and experimental data (Figs 1 and 3). Excessive consumption of specific dietary drivers favors metabolic inflammation and insulin resistance, and dietary modulation plays a significant role in risk of T2D and NAFLD.…”

Liver fat storage pathways: methodologies and dietary effects

“…Dietary fat uptake is commonly measured by using FA tracers enriched with the stable carbon isotope 13 C [ 7 , 8 , 9 ▪▪ , 10 ▪▪ ] or deuterium ( 2 H) [ 5 , 6 , 11 , 12 ], due to their low natural abundance (1.1 and 0.015%, respectively). Usually, a meal with 13 C-labeled palmitate, deuterated tri-palmitate or [ 2 H 35 ] stearate is given to trace incorporation of meal fat in VLDL triglyceride (VLDL-TG) [ 5 – 8 , 9 ▪▪ , 10 ▪▪ , 11 , 12 ]. The FA composition and the tracer enrichment were shown to be similar in VLDL-TG and liver triglyceride (determined from liver biopsies), therefore the tracer enrichment of plasma VLDL-TGs can be used as a surrogate for liver fat enrichment and can be used to determine hepatic storage of meal fat [ 5 , 13 ].…”