Metabolic regulation of fatty acid esterification and effects of conjugated linoleic acid on glucose homeostasis in pig hepatocytes

Conde-Aguilera, Jose Alberto; Lachica, M.; Nieto, R.; Fernández‐Fígares, I.

doi:10.1017/s1751731111001613

Cited by 12 publications

(8 citation statements)

References 53 publications

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“…As supplementation of trans-10,cis-12 CLA, as well as rumen-protected fat, results in a glucose-sparing effect, hepatic gene expression of G6Pase might be a key factor in regulating eGP by reducing glucose delivery to the circulation. Interestingly, CLA treatment decreased gluconeogenesis in porcine hepatocytes, possibly due to increased hepatic insulin sensitivity (Conde-Aguilera et al, 2012). However, it is not clear whether this is also the case in bovine hepatocytes, and, as discussed above, CLA may have not changed insulin sensitivity in our study.…”

Section: Cla Effects On Glucose Metabolismmentioning

confidence: 46%

Supplementation of conjugated linoleic acid in dairy cows reduces endogenous glucose production during early lactation

Hötger

Hammon

Weber

et al. 2013

Journal of Dairy Science

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Trans-10,cis-12 conjugated linoleic acid (CLA) supplementation causes milk fat depression in dairy cows, but CLA effects on glucose metabolism are not clear. The objective of the study was to investigate glucose metabolism, especially endogenous glucose production (eGP) and glucose oxidation (GOx), as well as hepatic genes involved in endogenous glucose production in Holstein cows supplemented either with 50 g of rumen-protected CLA (9% trans-10,cis-12 and 10% cis-9,trans-11; CLA; n = 10) or 50 g of control fat (24% C18:2; Ctrl; n = 10) from wk 2 before parturition to wk 9 of lactation. Animal performance data were recorded and blood metabolites and hormones were taken weekly from 2 wk before to 12 wk after parturition. During wk 3 and 9 after parturition, glucose tolerance tests were performed and eGP and GOx were measured by [U-13 C] glucose infusion. Liver biopsies were taken at the same time to measure total fat and glycogen concentrations and gene expression of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and carnitine palmitoyl-transferase 1. Conjugated linoleic acid feeding reduced milk fat, but increased milk lactose output; milk yield was higher starting 5 wk after parturition in CLA-fed cows than in Ctrl-fed cows. Energy balance was more negative during CLA supplementation, and plasma concentrations of glucose were higher immediately after calving in CLAfed cows. Conjugated linoleic acid supplementation did not affect insulin release during glucose tolerance tests, but reduced eGP in wk 3, and eGP and GOx increased with time after parturition. Hepatic gene expression of cytosolic phosphoenolpyruvate carboxykinase tended to be lower in CLA-fed cows than in Ctrl-fed cows. In spite of lower eGP in CLA-fed cows, lactose output and plasma glucose concentrations were greater in CLA-fed cows than in Ctrl-fed cows. This suggests a CLA-related glucose sparing effect most likely due to lower glucose utilization for milk fat synthesis and probably because of a more efficient whole-body energy utilization in CLA-fed cows.

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Section: Cla Effects On Glucose Metabolismmentioning

confidence: 46%

Supplementation of conjugated linoleic acid in dairy cows reduces endogenous glucose production during early lactation

Hötger

Hammon

Weber

et al. 2013

Journal of Dairy Science

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“…Accordingly, Francini et al [52] showed that in Wistar rats given drinking water containing 10% fructose over three weeks, glycogen stores in the liver increased. However, in more advanced stages, the large input of fructose in the liver produces an allosteric negative regulation of the enzyme phosphofructokinase, reducing the uptake of glucose by the liver [53], increasing hepatic gluconeogenesis, and inducing a high intrahepatic accumulation of lipids, which, in turn, occupy a large volume within hepatocytes and disorganize the hepatic structure and functions such as glycogen storage, as well as reducing hepatic IGF-1 synthesis and inducing hepatic IR [50,54]. Our data showing an increase in glycogen stores of the Young – FRU group, unlike the results for the Adult – FRU group, suggest that these groups are at different stages of MS and hepatic IR induced by fructose.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats

et al. 2013

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BackgroundThe metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages.MethodsYoung (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated.ResultsIn young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats.ConclusionsOur data show that FRU diet in adult rats causes biggest change on metabolism of serum lipids and lipid accumulation in liver and kidney, while the FAT diet in young rats induces elevation of MAP and HR and higher increased visceral lipid stores, constituting the best nutritional interventions to induce MS in rats.

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“…After stunning by electric shock they were exsanguinated and livers were immediately excised, the left lateral lobe removed and transported from the abattoir to the cell culture laboratory in ice cold sterile transport media (Minimum Essential Medium Eagle with Hanks' salts Sigma M9288, 4.46 mM NaCO 3 H, 0.2 mM NaOH) as quick as possible (5 min). Hepatocytes were isolated essentially as published by Conde-Aguilera et al (2012). Viability of isolated hepatocytes from animals was 81.4 ± 4.7% (trypan blue dye exclusion) and cell yield from each liver preparation was 4.9 ± 0.5 × 10 8 viable hepatocytes (n = 18).…”

Section: Isolation Of Liver Cells and Cell Culturementioning

confidence: 99%

“…Protein determination Protein in cell homogenates was determined by a modified Lowry procedure as described by Conde-Aguilera et al (2012). All data were normalized to protein content.…”

Section: Urea Synthesismentioning

confidence: 99%

Metabolic differences in hepatocytes of obese and lean pigs

González-Valero

Rodríguez-López

Lachica

et al. 2014

Animal

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There are important differences in terms of metabolic activity, energy utilization and capacity of protein and fat deposition when Iberian and modern pigs are compared. Primary culture of hepatocytes was used to evaluate hepatic function and sensitivity to hormones between breeds without the interference of circulating blood factors. Hepatocytes were isolated from pure Iberian (n = 10) and Landrace (n = 8) pigs of similar BW (24.5 ± 12.1 and 32.9 ± 6.1 kg BW, respectively), by collagenase perfusion. Monolayers were established in medium containing fetal bovine serum for 1 day and switched to serum-free medium for the remainder of the culture period. Hepatocytes were maintained in William's E supplemented with β-mercaptoethanol (0.1 mM), glutamine (2 mM), antibiotics (gentamicin, penicillin, streptomycin and amphotericin B), dimethyl sulfoxide (1 µg/ml), dexamethasone (10 −8 M), insulin (0.173 and 17.3 nM) and glucagon (0.287, 2.87 and 28.7 nM) for 24 to 48 h. Gluconeogenesis (GNG), glycogen degradation, triglycerides (TG) content and esterification, β-hydroxybutyrate (BHB) synthesis, IGF-1 synthesis, albumin and urea synthesis were determined. Iberian pigs had greater capacity of GNG than Landrace (24%, P < 0.05), although no difference in glycogen degradation was found (P > 0.10). TG content and esterification tended to be lower in hepatocytes from Iberian compared with Landrace pigs (12% and 31%, respectively; 0.10 < P < 0.05). Furthermore, addition of free fatty acids (CLA or linoleic acid, 0.2 mM) increased TG content (64%, P < 0.001) although no difference between fatty acids was found. When free fatty acids were compared, a trend toward increased esterification (41%, P = 0.078) was found for CLA. Although glucagon stimulated and insulin inhibited BHB synthesis, no difference between breeds was found (P > 0.10). IGF-1 synthesis was diminished in hepatocytes from Iberian compared with Landrace pigs (16%, P < 0.05). On the contrary, rate of albumin synthesis was greater in Iberian compared with Landrace pigs (58%, P < 0.05). Finally, the capacity of urea synthesis was lower in hepatocytes of Iberian compared with Landrace pigs (37%, P < 0.05). When ammonia was added to the media, urea concentration increased (648%, 1108% and 2791% when 0 mM was compared with 2.5, 5 and 10 mM, respectively). Urea synthesis increased on increasing ammonia content (55% and 325% when 0 mM was compared with 5 and 10 mM, respectively; P < 0.0001). In conclusion, the genetic background accounts for important differences in protein and energy metabolism pathways found in primary culture of hepatocytes from lean and obese pigs.Keywords: hepatocytes, metabolism, pig ImplicationsSeveral studies have shown the existence of numerous dissimilarities in metabolic activity between Iberian and modern pig breeds that might be explained by genotypic differences. Primary hepatocyte cultures are a valuable tool to study specific metabolic liver functions, without the interference of changing levels of metabolites and hormones found in vivo. These...

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Metabolic regulation of fatty acid esterification and effects of conjugated linoleic acid on glucose homeostasis in pig hepatocytes

Cited by 12 publications

References 53 publications

Supplementation of conjugated linoleic acid in dairy cows reduces endogenous glucose production during early lactation

Supplementation of conjugated linoleic acid in dairy cows reduces endogenous glucose production during early lactation

Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats

Metabolic differences in hepatocytes of obese and lean pigs

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