Response of hepatic lipid and glucose metabolism to a mixture or single fatty acids: Possible presence of fatty acid-sensing mechanisms

ABSTRACT To elucidate the hypolipacidaemic effect of insulin in ducks, its action on the uptake of free fatty acids (FFA) by duck hepatocytes was determined. At low doses (10 mu./l) insulin stimulated FFA uptake. This effect was not observed with higher doses of insulin (20, 30 and 50 mu./l). Growth hormone at physiological concentrations and corticosterone (14·4 nmol/l) decreased basal activity, probably by reducing glucose metabolism and consequently α-glycerophosphate (α-GP) supply. Insulin was able to reverse the inhibition induced by GH and corticosterone on both FFA uptake and α-GP production. These results therefore suggest that the hypolipacidaemic effect of insulin may be partly mediated by its action on hepatic FFA uptake. J. Endocr. (1984) 102, 381–386

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Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet-Induced Accumulation of Lipid in the Liver of ApoE−/− Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6256802 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Liang Liu ◽

Qinling Hu ◽

Huihui Wu ◽

Xiujing Wang ◽

Chao Gao ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Lipid Metabolism ◽

Liver Disease ◽

Inflammatory Responses ◽

Elevated Serum ◽

Serum Levels ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Fa Composition

Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE−/− mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks. After treatment, the serum and hepatic FA compositions, serum biochemical parameters, liver injury, and hepatic lipid metabolism-related gene expression were determined. Our results demonstrated that dietary DHA/EPA changed serum and hepatic FA composition by increasing contents of n-6 and n-3 PUFAs and decreasing amounts of monounsaturated fatty acids (MUFAs) and the n-6/n-3 ratio. Among the three DHA/EPA groups, the DHA/EPA 2 : 1 group tended to raise n-3 PUFAs concentration and lower the n-6/n-3 ratio in the liver, whereas DHA/EPA 1 : 2 tended to raise n-6 PUFAs concentration and improve the n-6/n-3 ratio. DHA/EPA supplementation reduced the hepatic impairment of lipid homeostasis, oxidative stress, and the inflammatory responses in HFD-fed mice. The DHA/EPA 2 : 1 group had lower serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol and higher levels of adiponectin than HFD group. The DHA/EPA 1 : 2 group had elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, without significant change the expression of genes for inflammation or hepatic lipid metabolism among the three DHA/EPA groups. The results suggest that DHA/EPA-enriched diet with an n-6/n-3 ratio of 4 : 1 may reverse HFD-induced nonalcoholic fatty liver disease to some extent by increasing n-6 and n-3 PUFAs and decreasing the amount of MUFAs and the n-6/n-3 ratio.

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Increased Glucose Metabolism and Glycerolipid Formation by Fatty Acids and GPR40 Receptor Signaling Underlies the Fatty Acid Potentiation of Insulin Secretion

Journal of Biological Chemistry ◽

10.1074/jbc.m113.531970 ◽

2014 ◽

Vol 289 (19) ◽

pp. 13575-13588 ◽

Cited By ~ 41

Author(s):

Mahmoud El-Azzouny ◽

Charles R. Evans ◽

Mary K. Treutelaar ◽

Robert T. Kennedy ◽

Charles F. Burant

Keyword(s):

Fatty Acids ◽

Insulin Secretion ◽

Fatty Acid ◽

Glucose Metabolism ◽

Receptor Signaling

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Peroxisome-proliferator-activated receptor-α (PPARα) deficiency leads to dysregulation of hepatic lipid and carbohydrate metabolism by fatty acids and insulin

Biochemical Journal ◽

10.1042/bj20011699 ◽

2002 ◽

Vol 364 (2) ◽

pp. 361-368 ◽

Cited By ~ 102

Author(s):

Mary C. SUGDEN ◽

Karen BULMER ◽

Geoffrey F. GIBBONS ◽

Brian L. KNIGHT ◽

Mark J. HOLNESS

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Carbohydrate Metabolism ◽

Plasma Insulin ◽

Hepatic Glycogen ◽

Peroxisome Proliferator ◽

Hepatic Lipogenesis ◽

Wild Type ◽

Peroxisome Proliferator Activated Receptor ◽

Hepatic Lipid

The aim of the present study was to determine whether peroxisome-proliferator-activated receptor-α (PPARα) deficiency disrupts the normal regulation of triacylglycerol (TAG) accumulation, hepatic lipogenesis and glycogenesis by fatty acids and insulin using PPARα-null mice. In wild-type mice, hepatic TAG concentrations increased (P<0.01) with fasting (24h), with substantial reversal after refeeding (6h). Hepatic TAG levels in fed PPARα-null mice were 2.4-fold higher than in the wild-type (P<0.05), increased with fasting, but remained elevated after refeeding. PPARα deficiency also impaired hepatic glycogen repletion (P<0.001), despite normal insulin and glucose levels after refeeding. Higher levels of plasma insulin were required to support similar levels of hepatic lipogenesis de novo (3H2O incorporation) in the PPARα-null mice compared with the wild-type. This difference was reflected by corresponding changes in the relationship between plasma insulin and the mRNA expression of the lipogenic transcription factor sterol-regulatory-element-binding protein-1c, and that of one of its known targets, fatty acid synthase. In wild-type mice, hepatic pyruvate dehydrogenase kinase (PDK) 4 protein expression (a downstream marker of altered fatty acid catabolism) increased (P<0.01) in response to fasting, with suppression (P<0.001) by refeeding. Although PDK4 up-regulation after fasting was halved by PPARα deficiency, PDK4 suppression after refeeding was attenuated. In summary, PPARα deficiency leads to accumulation of hepatic TAG and elicits dysregulation of hepatic lipid and carbohydrate metabolism, emphasizing the importance of precise control of lipid oxidation for hepatic fuel homoeostasis.

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Effects of cell density on in vitro glucose metabolism by isolated adipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.3.e361 ◽

1993 ◽

Vol 264 (3) ◽

pp. E361-E366 ◽

Cited By ~ 3

Author(s):

M. Digirolamo ◽

S. V. Thacker ◽

S. K. Fried

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Glucose Metabolism ◽

Cell Density ◽

Acid Concentration ◽

Cell Concentration ◽

Fatty Acid Concentration ◽

Fat Cell ◽

Cell Concentrations

We studied the effect of variable isolated fat cell concentrations (from 0.17 to 1.25 x 10(6) cells/ml) on rate and pattern of basal and insulin-stimulated glucose metabolism by rat epididymal fat cells. Cell concentration did not affect total glucose utilization, but high cell concentrations increased the absolute and relative conversion of glucose to CO2 and glyceride-fatty acids by two- to threefold and decreased the conversion to lactate, pyruvate, and glyceride-glycerol when compared with values observed at low cell concentration. When effects of adenosine deaminase (ADA) and N-6(2-phenylisopropyl)adenosine (PIA) were examined, addition of ADA to incubated cells produced no significant changes in the rate or pattern of adipocyte glucose metabolism; PIA had a slight and uniform effect on the conversion of glucose to its metabolic products and minimal effect on insulin-stimulated glucose metabolism. Medium free fatty acid concentration did not change during the incubation at various cell density, but intracellular free fatty acids were found to be inversely related to fat cell density in the medium. Thus a variable fat cell density influences the pattern of adipocyte glucose metabolism in vitro. This effect may be due to variable rates of lipolysis and resulting changes in intracellular fatty acid concentration rather than to adenosine per se. This work has practical implications in the need to define cell density when carrying out in vitro measurements of adipocyte glucose conversion to products.

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Hypothalamic mechanisms linking fatty acid sensing and food intake regulation in rainbow trout

Journal of Molecular Endocrinology ◽

10.1530/jme-17-0148 ◽

2017 ◽

Vol 59 (4) ◽

pp. 377-390 ◽

Cited By ~ 13

Author(s):

Cristina Velasco ◽

Cristina Otero-Rodiño ◽

Sara Comesaña ◽

Jesús M Míguez ◽

José L Soengas

Keyword(s):

Fatty Acids ◽

Transcription Factors ◽

Fatty Acid ◽

Rainbow Trout ◽

Food Intake ◽

Food Intake Regulation ◽

Intake Regulation ◽

First Time ◽

Specific Inhibitors ◽

Fatty Acid Sensing

We assessed in rainbow trout hypothalamus the effects of oleate and octanoate on levels and phosphorylation status of two transcription factors, FoxO1 and CREB, possibly involved in linking activation of fatty acid sensing with modulation of food intake through the expression of brain neuropeptides. Moreover, we assessed changes in the phosphorylation status of three proteins possibly involved in modulation of these transcription factors such as Akt, AMPK and mTOR. In a first experiment, we evaluated, in pools of hypothalamus incubated for 3 h and 6 h at 15°C in a modified Hanks’ medium containing 100 or 500 µM oleate or octanoate, the response of fatty acid sensing, neuropeptide expression and phosphorylation status of proteins of interest. The activation of fatty acid sensing and enhanced anorectic potential occurred in parallel with the activation of Akt and mTOR, and the inhibition of AMPK. The changes in these proteins would relate to a neuropeptide expression through changes in the phosphorylation status of transcription factors under their control, such as CREB and FoxO1, which displayed inhibitory (CREB) or activatory (FoxO1) responses when tissues were incubated with oleate or octanoate. In a second experiment, we incubated hypothalamus for 6 h with 500 µM oleate or octanoate alone or in the presence of specific inhibitors of Akt, AMPK, mTOR, CREB or FoxO1. The presence of inhibitors counteracted the effects of oleate or octanoate on the phosphorylation status of the proteins of interest. The results support, for the first time in fish, the involvement of these proteins in the regulation of food intake by fatty acids.

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Dietary trans-Fatty Acid Induced NASH is Normalized Following Loss of trans-Fatty Acids from Hepatic Lipid Pools

Lipids ◽

10.1007/s11745-012-3709-7 ◽

2012 ◽

Vol 47 (10) ◽

pp. 941-950 ◽

Cited By ~ 27

Author(s):

Brent A. Neuschwander-Tetri ◽

David A. Ford ◽

Sahaja Acharya ◽

George Gilkey ◽

Metin Basaranoglu ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Trans Fatty Acid ◽

Trans Fatty Acids ◽

Hepatic Lipid

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Comparison of the flux of carbon to hepatic glycogen deposition and fatty acid and cholesterol synthesis on refeeding rats fed ad libitum or meal-fed rats with a chow-diet meal

Biochemical Journal ◽

10.1042/bj2570607 ◽

1989 ◽

Vol 257 (2) ◽

pp. 607-610 ◽

Cited By ~ 7

Author(s):

F V Pallardo ◽

D H Williamson

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Cholesterol Synthesis ◽

Lipid Synthesis ◽

Hepatic Glycogen ◽

Chow Diet ◽

Hepatic Lipid ◽

Exogenous Glucose ◽

Ad Libitum ◽

Glycogen Deposition

Meal-fed rats and rats fed ad libitum had similar rates of hepatic glycogen deposition on refeeding with a chow meal. In contrast, the rate of hepatic lipid synthesis (cholesterol plus fatty acids) was 6-fold higher on refeeding in the meal-fed group compared with the ‘ad libitum’ group. There were no significant differences in the gastrointestinal or hepatic contents of glucose or lactate between the two groups. It is suggested that in the meal-fed group exogenous glucose may be directly converted into glycogen, whereas the substrate for lipid synthesis is a C3 unit.

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Early Effects of Sleeve Gastrectomy (SG) on Systemic and Organ-Specific Dietary Fatty Acid Uptake, Postprandial Free Fatty Acids (FFA), and Glucose Metabolism in Type 2 Diabetes (T2D)

Diabetes ◽

10.2337/db18-150-or ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 150-OR

Author(s):

ANNE-MARIE CARREAU ◽

CHRISTOPHE NOLL ◽

BRIGITTE GUERIN ◽

LAURENT BIERTHO ◽

ERIC E. TURCOTTE ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Sleeve Gastrectomy ◽

Fatty Acid ◽

Glucose Metabolism ◽

Fatty Acid Uptake ◽

Acid Uptake ◽

Organ Specific ◽

Early Effects

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The response of adipocyte glucose metabolism and fatty acid release to adenosine deaminase, insulin and perifusion. Investigation of intermediary metabolism by perifusion

Biochemical Journal ◽

10.1042/bj2510733 ◽

1988 ◽

Vol 251 (3) ◽

pp. 733-737

Author(s):

R D Harper

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Glucose Metabolism ◽

Adenosine Deaminase ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Intermediary Metabolism ◽

Glucose Incorporation ◽

Fatty Acid Release ◽

Acid Release

Adipocytes incubated with adenosine deaminase (ADA) showed: (1) increased amounts of fatty acids in the medium; (2) increased glucose incorporation into acylglycerol glycerol; (3) decreased glucose incorporation into acylglycerol fatty acids; (4) a co-ordinate decrease in the sensitivity of lipolysis and glucose incorporation into acylglycerol to insulin; (5) similar effects on glucose incorporations in perifused and normal incubations. The decrease in fatty acid synthesis by perfusion was found to be dependent on the presence of insulin or fatty acids, and independent of the effects of ADA. The significance of the effects of perifusion, ADA and insulin are discussed in relation to effects of fatty acids.

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