Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet

Hernandez, Teri L.; Sutherland, Julie P; Wolfe, Pamela; Allian-Sauer, Marybeth; Capell, Warren H.; Talley, Natalie D; Wyatt, Holly R.; Foster, Gary D.; Hill, James O.; Eckel, Robert H.

doi:10.3945/ajcn.2009.27909

Cited by 56 publications

(59 citation statements)

References 41 publications

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“…1). The latter triggers, at least if the amount of carbohydrate is sufficiently low (<60 g/day), an increase in fasting and postprandial NEFAs as well as ketone bodies [7]. The decrease in insulin can be predicted to decrease liver fat by diverting NEFA flux from lipogenesis to oxidation, although these processes have not been measured directly in humans [8].…”

Section: H-mrs Proton Magnetic Resonance Spectroscopymentioning

confidence: 99%

Type 2 diabetes: remission in just a week

Yki‐Järvinen

2011

Diabetologia

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Section: H-mrs Proton Magnetic Resonance Spectroscopymentioning

confidence: 99%

Type 2 diabetes: remission in just a week

Yki‐Järvinen

2011

Diabetologia

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“…It has been observed that NEFA profiles in individuals with obesity or hyperlipidaemia are substantially altered compared with healthy individuals; such changes are regarded as an important risk factor for type 2 diabetes [7,9]. Palmitic acid is widely employed as a representative fatty acid to investigate the relationship between SFA and type 2 diabetes because it accounts for the highest percentage of dietary NEFA for the human body.…”

Section: Introductionmentioning

confidence: 99%

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

Hao

et al. 2016

Diabetologia

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Aims/hypothesis Serum stearic acid (C18:0) is elevated in individuals with hyperlipidaemia and type 2 diabetes. However, the lipotoxicity induced by increased stearic acid in beta cells has not been well described. This study aimed to examine the adverse effects of stearic acid on beta cells and the potential mechanisms through which these are mediated. Methods Three groups of C57BL/6 mice were fed a normal diet or a high-stearic-acid/high-palmitic-acid diet for 24 weeks, respectively. The microRNA (miR) profiles of islets were determined by microarray screening. Islet injury was detected with co-staining using the TUNEL assay and insulin labelling. A lentiviral vector expressing anti-miRNA-34a-5p oligonucleotide (AMO-34a-5p) was injected into mice via an intraductal pancreatic route. Results In both mouse islets and cultured rat insulinoma INS-1 cells, stearic acid exhibited a stronger lipotoxic role than other fatty acids, owing to repression of B cell CLL/ lymphoma 2 (BCL-2) and BCL-2-like 2 (BCL-W) by stearic acid stimulation of miR-34a-5p. The stearic-acid-induced lipotoxicity and reduction in insulin secretion were alleviated by AMO-34a-5p. Further investigations in INS-1 cells revealed that p53 was involved in stearic-acid-induced elevation of miR-34a-5p, owing in part to activation of protein kinaselike endoplasmic reticulum kinase (PERK). Conversely, silencing PERK alleviated stearic-acid-induced p53, miR-34a-5p and lipotoxicity. Conclusions/interpretation These findings provide new insight for understanding the molecular mechanisms underlying not only the deleterious impact of stearic-acid-induced lipotoxicity but also apoptosis in beta cells and progression to type 2 diabetes.

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“…7 In contrast to reported positive health effects of carbohydrate restriction, increased free fatty acids and LDL cholesterol were observed in a recent experimental study. 8 From a long-term perspective, the health effects of carbohydrate-restricted diets are not well known. Increased all-cause, cardiovascular and cancer mortality demonstrated in cohort studies seem to contradict any sustainable benefit from a LCHP diet in the general population.…”

Section: Introductionmentioning

confidence: 99%

“…Increased all-cause, cardiovascular and cancer mortality demonstrated in cohort studies seem to contradict any sustainable benefit from a LCHP diet in the general population. 9 --12 Elevated LDL cholesterol as a result of carbohydrate-restricted diet 8 may contribute to atherosclerosis and CVD. Type of carbohydrates (for example, complex, simple) and proteins (for example, animal, vegetable) consumed may also affect risk associations.…”

Section: Introductionmentioning

confidence: 99%

Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort

et al. 2012

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BACKGROUND/OBJECTIVE: Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality. SUBJECTS/METHODS: This is a population-based cohort study on adults in the northern Swedish county of Västerbotten. In 37 639 men (1460 deaths) and 39 680 women (923 deaths) from the population-based Västerbotten Intervention Program, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create an LCHP score (2 --20 points). Sex-specific hazard ratios (HR) were calculated by Cox regression. RESULTS: Median intakes of carbohydrates, protein and fat in subjects with LCHP scores 2 --20 ranged from 61.0% to 38.6%, 11.3% to 19.2% and 26.6% to 41.5% of total energy intake, respectively. High LCHP score (14 --20 points) did not predict all-cause mortality compared with low LCHP score (2 --8 points), after accounting for saturated fat intake and established risk factors (men: HR for high vs low 1.03 (95% confidence interval (CI) 0.88 --1.20), P for continuous ¼ 0.721; women: HR for high vs low 1.10 (95% CI 0.91 --1.32), P for continuous ¼ 0.229). For cancer and cardiovascular disease, no clear associations were found. Carbohydrate intake was inversely associated with all-cause mortality, though only statistically significant in women (multivariate HR per decile increase 0.95 (95% CI 0.91 --0.99), P ¼ 0.010). CONCLUSION: Our results do not support a clear, general association between LCHP score and mortality. Studies encompassing a wider range of macronutrient consumption may be necessary to detect such an association.

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Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet

Abstract: Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs.

Cited by 56 publications

References 41 publications

Type 2 diabetes: remission in just a week

Type 2 diabetes: remission in just a week

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort

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