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Oxidized LDL and Fructosamine Associated with Severity of Coronary Artery Atherosclerosis in Insulin Resistant Pigs Fed a High Fat/High NaCl Diet.

Nichols TC, Merricks EP, Bellinger DA, Raymer RA, Yu J, Lam D, Koch GG, Busby WH, Clemmons DR - PLoS ONE (2015)

Bottom Line: Insulin resistance was not associated with atherosclerosis severity.Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis.In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

ABSTRACT

Background: Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin-sensitive controls but the mechanisms that mediate this atherosclerosis phenotype are unknown.

Research objective: To determine the metabolic parameters that associate with the severity of coronary atherosclerosis in insulin resistant pigs fed a high fat/high NaCl diet.

Key methods: The primary endpoint was severity of coronary atherosclerosis in adult pigs (Sus scrofa, n = 37) fed a high fat diet that also contained high NaCl (56% above recommended levels) for 1 year.

Principal findings: Twenty pigs developed severe and diffuse distal coronary artery atherosclerosis (i.e., severe = intimal area as a percent medial area > 200% in at least 2 coronary artery cross sections and diffuse distal = intimal area as a percent medial area ≥ 150% over 3 sections separated by 2 cm in the distal half of the coronary artery). The other 17 pigs had substantially less coronary artery atherosclerosis. All 37 pigs had blood pressure in a range that would be considered hypertensive in humans and developed elevations in total and LDL and HDL cholesterol, weight gain, increased backfat, and increased insulin resistance (Bergman Si) without overt diabetes. Insulin resistance was not associated with atherosclerosis severity. Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis. Most importantly, the 20 high fat/high NaCl diet-fed pigs with severe and diffuse distal coronary artery atherosclerosis had substantially greater increases (p< 0.05) in oxidized LDL (oxLDL) and fructosamine consistent with increased protein glycation.

Conclusion: In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis.

No MeSH data available.


Related in: MedlinePlus

Study Design.The 42 pigs entered into this study are listed according to the diet they were fed, genotype (NL = normal, FH het = FH heterozygous) and gender.
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pone.0132302.g001: Study Design.The 42 pigs entered into this study are listed according to the diet they were fed, genotype (NL = normal, FH het = FH heterozygous) and gender.

Mentions: All pigs were produced and maintained in the same environmental conditions at the Francis Owen Blood Research Laboratory at the University of North Carolina at Chapel Hill. The background was Spotted Poland/China and Yorkshire crosses. Male and female pigs from the following two genotypes were used: (1) normocholesterolemic or (2) heterozygous familial hypercholesterolemic (FH) that have a recessive inheritance pattern.[19–21] Both genotypes of pigs are normocholesterolemic at baseline and only exhibit hypercholesterolemia when fed a high fat diet. In addition to being identified by normal cholesterol levels, FH heterozygotes are also identified from litters produced by known sires and dams with normal LDL receptor sequences or carrying the FH mutation, a missense mutation in a single base pair (C253➔ T253) of the LDL receptor that results in an arginine94 to cysteine94 mutation, located in the region that corresponds to exon 4 in the human ligand binding domain.[19–21] Pigs were maintained in agricultural style Hog Slats Inc buildings with ambient light and dark cycles, free access to water, with a temperature range of 55 to 85 degrees F. All pigs were checked daily for food consumption and general health issues. The UNC Division of Laboratory Animal Medicine provided regular veterinarian oversight. Forty-two pigs were entered into the year long study as they became available (Fig 1). Thirty-seven pigs were fed a high fat/high NaCL diet for one year: 16 normal (10 males, 6 females) and 21 heterozygous FH (10 males, 11 females). Five pigs were fed regular pig chow: 2 normal (1 male, 1 female) and 3 heterozygous FH (1 male, 2 females). The mean age at study entry was 3.2 ± 1.6 years.


Oxidized LDL and Fructosamine Associated with Severity of Coronary Artery Atherosclerosis in Insulin Resistant Pigs Fed a High Fat/High NaCl Diet.

Nichols TC, Merricks EP, Bellinger DA, Raymer RA, Yu J, Lam D, Koch GG, Busby WH, Clemmons DR - PLoS ONE (2015)

Study Design.The 42 pigs entered into this study are listed according to the diet they were fed, genotype (NL = normal, FH het = FH heterozygous) and gender.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492503&req=5

pone.0132302.g001: Study Design.The 42 pigs entered into this study are listed according to the diet they were fed, genotype (NL = normal, FH het = FH heterozygous) and gender.
Mentions: All pigs were produced and maintained in the same environmental conditions at the Francis Owen Blood Research Laboratory at the University of North Carolina at Chapel Hill. The background was Spotted Poland/China and Yorkshire crosses. Male and female pigs from the following two genotypes were used: (1) normocholesterolemic or (2) heterozygous familial hypercholesterolemic (FH) that have a recessive inheritance pattern.[19–21] Both genotypes of pigs are normocholesterolemic at baseline and only exhibit hypercholesterolemia when fed a high fat diet. In addition to being identified by normal cholesterol levels, FH heterozygotes are also identified from litters produced by known sires and dams with normal LDL receptor sequences or carrying the FH mutation, a missense mutation in a single base pair (C253➔ T253) of the LDL receptor that results in an arginine94 to cysteine94 mutation, located in the region that corresponds to exon 4 in the human ligand binding domain.[19–21] Pigs were maintained in agricultural style Hog Slats Inc buildings with ambient light and dark cycles, free access to water, with a temperature range of 55 to 85 degrees F. All pigs were checked daily for food consumption and general health issues. The UNC Division of Laboratory Animal Medicine provided regular veterinarian oversight. Forty-two pigs were entered into the year long study as they became available (Fig 1). Thirty-seven pigs were fed a high fat/high NaCL diet for one year: 16 normal (10 males, 6 females) and 21 heterozygous FH (10 males, 11 females). Five pigs were fed regular pig chow: 2 normal (1 male, 1 female) and 3 heterozygous FH (1 male, 2 females). The mean age at study entry was 3.2 ± 1.6 years.

Bottom Line: Insulin resistance was not associated with atherosclerosis severity.Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis.In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

ABSTRACT

Background: Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin-sensitive controls but the mechanisms that mediate this atherosclerosis phenotype are unknown.

Research objective: To determine the metabolic parameters that associate with the severity of coronary atherosclerosis in insulin resistant pigs fed a high fat/high NaCl diet.

Key methods: The primary endpoint was severity of coronary atherosclerosis in adult pigs (Sus scrofa, n = 37) fed a high fat diet that also contained high NaCl (56% above recommended levels) for 1 year.

Principal findings: Twenty pigs developed severe and diffuse distal coronary artery atherosclerosis (i.e., severe = intimal area as a percent medial area > 200% in at least 2 coronary artery cross sections and diffuse distal = intimal area as a percent medial area ≥ 150% over 3 sections separated by 2 cm in the distal half of the coronary artery). The other 17 pigs had substantially less coronary artery atherosclerosis. All 37 pigs had blood pressure in a range that would be considered hypertensive in humans and developed elevations in total and LDL and HDL cholesterol, weight gain, increased backfat, and increased insulin resistance (Bergman Si) without overt diabetes. Insulin resistance was not associated with atherosclerosis severity. Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis. Most importantly, the 20 high fat/high NaCl diet-fed pigs with severe and diffuse distal coronary artery atherosclerosis had substantially greater increases (p< 0.05) in oxidized LDL (oxLDL) and fructosamine consistent with increased protein glycation.

Conclusion: In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis.

No MeSH data available.


Related in: MedlinePlus