High-fructose and high-fat diet-induced insulin resistance enhances atherosclerosis in Watanabe heritable hyperlipidemic rabbits

ObjectivesIn this study, we investigated whether a high-fat diet (HFD) affected the bone implant connection (BIC) in peri-implant bone.Materials and MethodsFour male rabbits were used in this study. Dental implant surgery was introduced into each tibia, and four implants were integrated into each animal. In both the normal diet (ND) group (n=2) and HFD group (n=2), 8 implants were integrated, for a total of 16 integrated implants. The animals continued with their respective diets for 12 weeks post-surgery. Afterward, the rabbits were sacrificed, and the BIC was assessed histomorphometrically.ResultsHistologic and histomorphometric analyses demonstrated that BIC was not impaired in the HFD group compared to the ND group.ConclusionWithin the limitations of this study, we found that HFD did not decrease the BIC in rabbit tibias.

show abstract

“…The HFD group was fed a chow diet supplemented with 10% coconut oil1015. The HFD was rich in fat, but with relatively less protein and fiber.…”

Section: Discussionmentioning

confidence: 99%

The effects of high-fat diet on implant osseointegration: an experimental study

Dündar

Yaman

Ozupek

et al. 2016

J Korean Assoc Oral Maxillofac Surg

View full text Add to dashboard Cite

show abstract

“…Obesity resulted in markedly increased serum creatinine kinase MB levels, a biomarker of cardiac tissue injury [7] . Exposing WHHL rabbits for 16 weeks to a HFFD versus a control diet however, did not affect body weight, but did lead to more SC and visceral fat accumulation, higher plasma and hepatic triglyceride levels, impaired glucose tolerance and accelerated aortic and coronary atherosclerosis [5] . In this study, we exposed WHHL-MI rabbits for one year to this HFD to slowly induce obesity, and to investigate whether these pathological conditions would enhance atherogenesis and affect cardiac function, leading to an accelerated mortality.…”

Section: Cardiac Function and Myocardial Fibrosismentioning

confidence: 87%

“…17-to 21-months old rabbits showed higher accumulation of RAM-11 (macrophages/monocytes)-positive mesenteric (MES) AT and lower plasma insulin levels as compared to adult WHHLMI rabbits [4] . 16 weeks exposure of WHHL rabbits to a high-fat and high-fructose diet (HFFD) induced an elevation of plasma lipid levels, impaired glucose tolerance, accumulation of AT and accelerated coronary atherosclerosis in these animals [5] .…”

Section: Introductionmentioning

confidence: 99%

Prolonged High-Fat Diet Feeding of WHHLMI Rabbits does Not Aggravate Metabolic or Cardiac Dysfunction

Hemmeryckx¹,

Feng²,

Frederix³

et al. 2018

JDO

View full text Add to dashboard Cite

Myocardial infarction (MI)-prone Watanabe hereditary hyperlipidemic (WHHLMI) rabbits were reported to spontaneously but slowly develop MI, associated with enhanced coronary atherosclerosis and metabolic syndrome features. Our aim was to accelerate these processes by exposing the rabbits to a high-fat diet (HFD) that was previously shown to induce insulin resistance and cardiac injury in rabbits. HFD feeding for one year was indeed associated with development of obesity (37% increases in body weight, as compared to 3.7% for control standard-fat diet, SFD). On HFD, liver weight and hepatic triglyceride content were significantly higher as compared to SFD, with mild steatosis. Glucose and insulin levels were not markedly different on SFD or HFD, however after 1 year of diet treatment, HFD-fed animals were more glucose intolerant as compared to SFD-fed rabbits. On SFD, the rabbits developed marked thoracic aorta stenosis and calcification of atherosclerotic lesions, which were not aggravated by HFD feeding. Cardiac function analysis by MRI and transthoracic echocardiography did not reveal significant differences between SFD-and HFD-fed rabbits. Thus, the metabolic and cardiac phenotype of WHHLMI rabbits was not aggravated by HFD feeding for one year, and the rabbits did not spontaneously develop diabetes or myocardial infarction.

show abstract

“…Thus, dysregulation of insulin signaling in VSMCs at the level of insulin receptor and IRS-2 may result in proliferative and proapoptotic phenotypes, which would enhance and exacerbate atherosclerosis, respectively. Although high fructose consumption is known to induce insulin resistance and promote atherosclerosis (D’Angelo et al, 2005; Lu et al, 2013; Ning et al, 2015), it is unknown as to how fructose uptake in VSMCs regulates insulin receptor signaling and proliferative phenotype.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, high fructose diet-induced insulin resistance results in exaggerated atherosclerosis and neointima formation with a significant increase in smooth muscle cell accumulation (Lu et al, 2013; Ning et al, 2015). Since platelet-derived growth factor (PDGF) is a potent mitogen released at the site of arterial injury (Barrett and Benditt, 1987; Heldin and Westermark, 1999; Rubin et al, 1988), it is likely that high fructose-induced increase in neointima formation may occur through enhanced PDGF receptor signaling.…”

Section: Introductionmentioning

confidence: 99%

High fructose-mediated attenuation of insulin receptor signaling does not affect PDGF-induced proliferative signaling in vascular smooth muscle cells

Osman

Poulose

Ganapathy

et al. 2016

European Journal of Pharmacology

View full text Add to dashboard Cite

Insulin resistance is associated with accelerated atherosclerosis. Although high fructose is known to induce insulin resistance, it remains unclear as to how fructose regulates insulin receptor signaling and proliferative phenotype in vascular smooth muscle cells (VSMCs), which play a major role in atherosclerosis. Using human aortic VSMCs, we investigated the effects of high fructose treatment on insulin receptor substrate-1 (IRS-1) serine phosphorylation, insulin versus platelet-derived growth factor (PDGF)-induced phosphorylation of Akt, S6 ribosomal protein, and extracellular signal-regulated kinase (ERK), and cell cycle proteins. In comparison with PDGF (a potent mitogen), neither fructose nor insulin enhanced VSMC proliferation and cyclin D1 expression. D-[14C(U)]fructose uptake studies revealed a progressive increase in fructose uptake in a time-dependent manner. Concentration-dependent studies with high fructose (5 to 25 mM) showed marked increases in IRS-1 serine phosphorylation, a key adapter protein in insulin receptor signaling. Accordingly, high fructose treatment led to significant diminutions in insulin-induced phosphorylation of downstream signaling components including Akt and S6. In addition, high fructose significantly diminished insulin-induced ERK phosphorylation. Nevertheless, high fructose did not affect PDGF-induced key proliferative signaling events including phosphorylation of Akt, S6, and ERK and expression of cyclin D1 protein. Together, high fructose dysregulates IRS-1 phosphorylation state and proximal insulin receptor signaling in VSMCs, but does not affect PDGF-induced proliferative signaling. These findings suggest that systemic insulin resistance rather than VSMC-specific dysregulation of insulin receptor signaling by high fructose may play a major role in enhancing atherosclerosis and neointimal hyperplasia.

show abstract

High-fructose and high-fat diet-induced insulin resistance enhances atherosclerosis in Watanabe heritable hyperlipidemic rabbits

Cited by 43 publications

References 26 publications

The effects of high-fat diet on implant osseointegration: an experimental study

The effects of high-fat diet on implant osseointegration: an experimental study

Prolonged High-Fat Diet Feeding of WHHLMI Rabbits does Not Aggravate Metabolic or Cardiac Dysfunction

High fructose-mediated attenuation of insulin receptor signaling does not affect PDGF-induced proliferative signaling in vascular smooth muscle cells

Contact Info

Product

Resources

About