Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial

Abstract

ContextSaturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms.ObjectiveTo investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DesignDouble-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SettingGeneral community.ParticipantsMen and women who are overweight or have obesity (n = 61).InterventionMuffins, high in either palm (SFA) or sunflower oil (PUFA), were added to the habitual diet.Main Outcome MeasuresLean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.ResultsBy design, body weight gain was similar in SFA (2.31 ± 1.38 kg) and PUFA (2.01 ± 1.90 kg) groups, P = 0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat, or total body fat compared with PUFA. SFA consistently increased, whereas PUFA reduced circulating ceramides, changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.ConclusionsSFA markedly induces liver fat and serum ceramides, whereas dietary PUFA prevents liver fat accumulation and reduces ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management

“…The SFA diet was associated with a marked increase in liver fat, probably because of an increase in de novo liver lipogenesis and an increase in lipolysis of adipose tissue. In contrast, unsaturated fat intake was associated with a decrease in lipolysis, preventing the accumulation of fat in the liver . The SFA diet has also been linked to impaired glutathione metabolism and an increase in oxidative stress, which leads to the progression of NAFLD .…”

“…Therefore, the ratio ω6/ω3 fats plays an important role in increasing the prevalence of chronic metabolic diseases (mostly a ω6/ω3 imbalance). Nevertheless, a double‐blind randomized trial showed that a long‐term hypercaloric diet rich in ω6 PUFA intake prevents liver fat accumulation in overweight individuals …”

“…In contrast, unsaturated fat intake was associated with a decrease in lipolysis, preventing the accumulation of fat in the liver. 4 The SFA diet has also been linked to impaired glutathione metabolism and an increase in oxidative stress, which leads to the progression of NAFLD. 5 However, at present, it is not clear whether different sources of SFA (for example, dairy vs meat) can have different effects on liver fat content.…”

“…Nevertheless, a double-blind randomized trial showed that a long-term hypercaloric diet rich in ω6 PUFA intake prevents liver fat accumulation in overweight individuals. 4 Several clinical trials have addressed the potential benefits of omega-3 PUFAs on NAFLD/NASH. A systematic review and meta-analysis of controlled intervention studies on the effects of ω3…”

Macrophages in the pathophysiology of NAFLD: The role of sex differences

“…Recent lipidomic studies are proposing a role for ceramides as promoters of insulin resistance 19 and, as a consequence, NAFLD genesis and progression 20 . Accordingly, randomized clinical trials (RCTs) showed that consumption of saturated fatty acids promotes ceramides generation and NAFLD development 21,22 . As opposite, consumption polyunsaturated fatty acids (PUFAs) seems to have a protective role, because long‐chain PUFAs might remove FFA excess from hepatocytes, improve insulin sensitivity and exert a direct anti‐inflammatory effect on neutrophil and macrophages 23 .…”