Three Weeks on a High-Fat Diet Increases Intrahepatic Lipid Accumulation and Decreases Metabolic Flexibility in Healthy Overweight Men

ArticleinThe Journal of Clinical Endocrinology and Metabolism 96(4):E691-5 · April 2011with8 Reads
Impact Factor: 6.21 · DOI: 10.1210/jc.2010-2243 · Source: PubMed

In rodents, high-fat diets increase intrahepatic lipid (IHL), but human studies are scarce. Our objective was to examine whether high-fat diets influence IHL, intramyocellular lipids (IMCL), and insulin resistance. Twenty overweight men were randomly allocated to low- or high-fat groups (age, 54.0 ± 2.3 and 56.4 ± 2.5 yr; body mass index, 29.3 ± 0.6 and 28.3 ± 0.5 kg/m(2), respectively). Both groups started with a 3-wk low-fat diet [15% energy (En%) as protein, 65 En% as carbohydrates, 20 En% as fat], after which half of the subjects switched to a 3-wk isocaloric high-fat diet (15 En% protein, 30 En% carbohydrates, 55 En% fat). After 3 and 6 wk, IHL and IMCL content were assessed by (1)H magnetic resonance spectroscopy and a muscle biopsy, and insulin sensitivity was studied using a hyperinsulinemic-euglycemic clamp. An additional liver scan was performed after 1 wk in the high-fat group. IHL decreased by 13% in the low-fat group and increased by 17% in high-fat group (P = 0.047). IMCL content was unaffected (P = 0.304). Insulin sensitivity was unaffected. At wk 3, IHL correlated negatively with insulin sensitivity (r = -0.584; P = 0.009, all subjects combined). Metabolic flexibility, defined as change in respiratory quotient upon insulin stimulation, was decreased after 3 wk of the high-fat diet (change in respiratory quotient was +0.02 ± 0.02 vs. -0.05 ± 0.1 in low-fat vs. high-fat group, P = 0.009). Basal plasma glucose increased after the high-fat diet (P = 0.038). Plasma parameters insulin, free fatty acids, high-sensitivity C-reactive protein, and liver enzymes and body weight were unaffected by diet. A 3-wk high-fat diet leads to IHL accumulation and a decreased metabolic flexibility, but insulin sensitivity is unaffected.

    • "Increased fat intake is a common finding in NAFLD patients [70,71], thus regulation of fat intake has been highlighted as potential target for therapeutic intervention to reduce hepatic lipids [72]. Contrasting results have been reported in human studies that have used a high fat diet to increase hepatic lipid content [73,74], whereas others have reported no effect of a high fat diet on hepatic lipids [75,76]. The lack of consistency is likely to be due to the duration of the studies (10 days–3 weeks) and the various forms of fat used (saturated, polyunsaturated (PUFA) and mono-unsaturated (MUFA)). "
    [Show abstract] [Hide abstract] ABSTRACT: The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed "dysbiosis", has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gut microbiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gut microbiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host-microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gut microbiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gut microbiota and how this impacts upon NAFLD prognosis.
    Full-text · Article · Mar 2016 · International Journal of Molecular Sciences
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    • "This is a first study to determine the effect of short-term HF-LC consumption with low-carbohydrate on exercise-induced GH response and IMCL content in healthy young males. Despite the fact that most previous studies recruited obese or diabetic subjects to determine dietary influences on endocrine or metabolic responses36373839, we selected healthy and young males, as a temporal (a few days) increase in fat intake is prevalent during daily life in this population. Therefore, we aimed to reveal the impact of short-term HF-LC consumption on endocrine and metabolic responses in healthy adults. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: The purpose of the present study was to examine the effects of 3. days isoenergetic high-fat/low-carbohydrate diet (HF-LC) relative to low-fat/high-carbohydrate diet (LF-HC) on the exercise-induced growth hormone (GH) response in healthy male subjects. Design: Ten healthy young males participated in this study. Each subject consumed the HF-LC (18±1% protein, 61±2% fat, 21±1% carbohydrate, 2720kcal per day) for 3 consecutive days after consuming the LF-HC (18±1% protein, 20±1% fat, 62±1% carbohydrate, 2755kcal per day) for 3 consecutive days. After each dietary intervention period, the hormonal and metabolic responses to an acute exercise (30min of continuous pedaling at 60% of V ˙O2max) were compared. The intramyocellular lipid (IMCL) contents in the vastus lateralis, soleus, and tibialis anterior were evaluated by proton magnetic resonance spectroscopy. Results: Serum GH concentrations increased significantly during the exercise after both the HF-LC and LF-HC periods (P <. 0.05). However, the exercise-induced GH response was not significantly different between the two periods. Fat utilization and lipolytic responses during the exercise were enhanced significantly after the HF-LC period compared with the LF-HC period. IMCL content did not differ significantly in any portion of muscle after the dietary interventions. Conclusions: We could not show that short-term HF-LC consumption changed significantly exercise-induced GH response or IMCL content in healthy young males.
    Full-text · Article · Sep 2015
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    • "The lack of an increase in hepatic triglyceride content on the HFD despite very high fat and saturated fat content is consistent with our previous findings using more modest fat content (45% calories from fat) [8]. These observations are contrary to previous studies that showed an increase in hepatic triglyceride content on a HFD compared to a LFD [6,7]. These previous studies used similarly high fat/saturated fat content and saw significant changes after only two or three weeks. "
    [Show abstract] [Hide abstract] ABSTRACT: Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNFα, IFN-γ) and oxidative stress (urinary F2-α isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change -2.13% (-3.74%, -0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-α isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress.
    Full-text · Article · Nov 2014 · Nutrients
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