Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling.

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The Use of Biomarkers as Alternatives to Current Animal Tests on Food Chemicals

Alternatives to Laboratory Animals ◽

10.1177/026119299802600411 ◽

1998 ◽

Vol 26 (4) ◽

pp. 421-480

Author(s):

Krys Bottrill

Keyword(s):

Animal Studies ◽

Developmental Toxicity ◽

Reproductive Toxicity ◽

In Vitro Test ◽

Animal Testing ◽

Dietary Biomarkers ◽

Recent Developments ◽

Mechanistic Basis ◽

The Three Rs

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on biomarkers of deleterious effects, since these are of greatest relevance to the subject of this review. The area of greatest activity was found to be that relating to biomarkers of mutagenic, genotoxic and carcinogenic effects. This is also one of the major areas of concern in considerations of the beneficial and deleterious effects of dietary components, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in the identification and development of biomarkers relating to certain classes of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and developmental toxicity, are less developed, and further investigation in these areas is required before a comprehensive biomarker strategy can be established. A criticism that recurs constantly in the biomarker literature is the lack of standardisation in the methods used, and the lack of reference standards for the purposes of validation and quality control. It is encouraging to note the growing acknowledgement of the need for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposals for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects of diet on health. The greatest potential is seen to be in the refinement of animal testing, in which biomarkers could serve as early and sensitive endpoints, in order to reduce the duration of the studies and also reduce the number of animals required. Biomarkers could also contribute to establishing a mechanistic basis for in vitro test systems and to facilitating their validation and acceptance. Finally, the increased information that could result from the incorporation of biomarker determinations into population studies could reduce the need for supplementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomarkers in relation to the Three Rs. It is emphasised, however, that further discussions will be required among toxicologists, epidemiologists and others researching the relationship between diet and health.

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In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22147502 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7502

Author(s):

Shelby L. Oke ◽

Kendrick Lee ◽

Rosemary Papp ◽

Steven R. Laviolette ◽

Daniel B. Hardy

Keyword(s):

Mitochondrial Dysfunction ◽

Animal Studies ◽

Weight Ratio ◽

Wistar Rat ◽

Hepatic Function ◽

Fetal Life ◽

Adult Rat ◽

Catch Up ◽

By Catch

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.

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Relationship Between High-Fructose Corn Syrup, Uric Acid, and Metabolic Syndrome

Journal of Pediatric Surgical Nursing ◽

10.1097/jps.0000000000000115 ◽

2016 ◽

Vol 5 (4) ◽

pp. 88

Author(s):

Monica J. McChesney

Keyword(s):

Metabolic Syndrome ◽

Uric Acid ◽

High Fructose Corn Syrup ◽

Corn Syrup ◽

High Fructose

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Prenatal exposure to persistent organic pollutants as a risk factor of offspring metabolic syndrome development during childhood

Reviews on Environmental Health ◽

10.1515/reveh-2020-0113 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Marlene Cervantes González

Keyword(s):

Metabolic Syndrome ◽

Organic Pollutants ◽

Prenatal Exposure ◽

Persistent Organic Pollutants ◽

Animal Studies ◽

Polychlorinated Biphenyl ◽

Environmental Pollutants ◽

Epidemiological Studies ◽

Experimental Findings

Abstract Persistent Organic Pollutants (POPs) are exogenous, artificially made chemicals that can disrupt the biological system of individuals and animals. POPs encompass a variety of chemicals including, dioxins, organochlorines (OCs), polychlorinated biphenyl (PCBs), and perfluoroalkyl substances (PFASs) that contain a long half-life and highly resistant to biodegradation. These environmental pollutants accumulate over time in adipose tissues of living organisms and alter various insulin function-related genes. Childhood Metabolic Syndrome (MetS) consists of multiple cardiovascular risk factors, insulin function being one of them. Over the years, the incidence of the syndrome has increased dramatically. It is imperative to explore the role of persistent organic pollutants in the development of Childhood Metabolic Syndrome. Some epidemiological studies have reported an association between prenatal exposure to POPs and offspring MetS development throughout childhood. These findings have been replicated in animal studies in which these pollutants exercise negative health outcomes such as obesity and increased waist circumference. This review discusses the role of prenatal exposure to POPs among offspring who develop MetS in childhood, the latest research on the MetS concept, epidemiological and experimental findings on MetS, and the POPs modes of action. This literature review identified consistent research results on this topic. Even though the studies in this review had many strengths, one major weakness was the usage of different combinations of MetS criteria to measure the outcomes. These findings elucidate the urgent need to solidify the pediatric MetS definition. An accurate definition will permit scientists to measure the MetS as a health outcome properly and allow clinicians to diagnose pediatric MetS and provide individualized treatment appropriately.

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Plasma glycerophospholipid profile, erythrocyte n–3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqab050 ◽

2021 ◽

Author(s):

Shuangshuang Chen ◽

Qingqing Wu ◽

Li Zhu ◽

Geng Zong ◽

Huaixing Li ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Animal Studies ◽

Plasma Concentrations ◽

Positive Association ◽

Community Dwelling ◽

P Value ◽

Total N ◽

Long Chain

ABSTRACT Background Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce. Objectives We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort. Methods A total of 1243 community-dwelling Chinese aged 50–70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Results After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16–1.30 per SD change; Bonferroni-corrected P < 0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P < 0.05]. This association was more pronounced in participants with lower erythrocyte total n–3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)< 0.05]. Conclusions Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.

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The Association Between Uric Acid and Hepatic Function Markers With the Metabolic Syndrome in Middle-aged, Overweight, and Obese People

The Endocrinologist ◽

10.1097/ten.0b013e318204d6e9 ◽

2010 ◽

Vol 20 (6) ◽

pp. 312-315

Author(s):

Angelos A. Evangelopoulos ◽

Natalia G. Vallianou ◽

Demosthenes B. Panagiotakos ◽

Aikaterini T. Georgiou ◽

Georgios A. Zacharias ◽

...

Keyword(s):

Metabolic Syndrome ◽

Uric Acid ◽

Hepatic Function ◽

Middle Aged ◽

Obese People ◽

The Metabolic Syndrome

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The analysis of surface saccharide profiles through fluorescein-labelled lectins in a rat pancreatic tissue with established metabolic syndrome model

Turkish Journal of Biochemistry ◽

10.1515/tjb-2017-0194 ◽

2018 ◽

Vol 44 (1) ◽

pp. 98-104

Author(s):

Yosun Mater ◽

Sule Beyhan-Ozdas

Keyword(s):

Metabolic Syndrome ◽

Metabolic Diseases ◽

Pancreatic Tissue ◽

Control Group ◽

High Fructose Diet ◽

Tissue Sections ◽

Membrane Surfaces ◽

High Fructose ◽

A Cell ◽

And Control

Abstract“Glycans”, which are generally referred as oligosaccharides and polysaccharides, are structures that are present on all cellular surfaces with proteins and lipids being attached to their basic chain structures. Many studies in the field of glycobiology have identified the various and complicated biological roles of these glycans which make them perfect molecules to use in labelling and selecting body cells specifically. This study aims at analyzing the modifications in saccharide units of glycans on a cell membrane surfaces of the pancreatic tissue of rats to which normal and metabolic syndrome (MetS) are established. To this end, a MetS model was created through a high fructose diet in Spraque Dawley breed of rats and the pancreatic tissue sections of the group with MetS and control group animals were evaluated comparatively. The targeted saccharide units were examined with Fluorescent Microscope by using two different Fluorescein (FITC) labelled lectins, namely Maackia amurensis-1 lectin [FITC-(MAL-I)] and the Wheat Germ Agglutinin (FITC-WGA). It was observed that FITC-MAL-1-labelled Galβ4GlcNAc units did not change much due to high- fructose diet. On the other hand, more GlcNAc, Neu5Ac and β-GlcNAc units which are labelled with FITC-WGA lectin increase in numbers in pancreatic sections of high fructose diet, compared to control group. Thus, a rapid and specific labelling method, which can identify surface saccharide sequences specifically, was developed. The method can be used in early diagnosis and/or treatment for metabolic diseases.

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