High-fructose diet leads to visceral adiposity and hypothalamic leptin resistance in male rats — do glucocorticoids play a role?

Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Renal changes were evaluated by measuring glomerulosclerosis, fibrosis, and arteriolar media/lumen (M/L) ratio.Results. The OA and FOA groups presented significantly hypertension (p<0.001). The OA group significantly increased (p<0.05) the percentage of glomerulosclerosis as well as the FOA group (p<0.001). When comparing NGN versus HGN, we observed a trend to a lower glomerulosclerosis in the latter. A higher arteriolar M/L ratio was observed in the OA (p<0.05) and FOA (p<0.001). Conclusion. Hyperuricemia conditions and a high-fructose diet favor blood pressure increase together with changes in the arteriolar media/lumen ratio and renal glomerular damage. These changes were more apparent in normogonadic animals.

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Kupffer cell depletion protects against the steatosis, but not the liver damage, induced by marginal-copper, high-fructose diet in male rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00285.2014 ◽

2015 ◽

Vol 308 (11) ◽

pp. G934-G945 ◽

Cited By ~ 8

Author(s):

Ming Song ◽

Dale A. Schuschke ◽

Zhanxiang Zhou ◽

Wei Zhong ◽

Jiayuan Zhang ◽

...

Keyword(s):

Fatty Liver ◽

Regulatory Element ◽

Critical Role ◽

Deionized Water ◽

Male Rats ◽

Sprague Dawley ◽

Deficient Diet ◽

High Fructose Diet ◽

Triglyceride Accumulation ◽

High Fructose

High-fructose feeding impairs copper status and leads to low copper availability, which is a novel mechanism in obesity-related fatty liver. Copper deficiency-associated hepatic iron overload likely plays an important role in fructose-induced liver injury. Excess iron in the liver is distributed throughout hepatocytes and Kupffer cells (KCs). The aim of this study was to examine the role of KCs in the pathogenesis of nonalcoholic fatty liver disease induced by a marginal-copper high-fructose diet (CuMF). Male weanling Sprague-Dawley rats were fed either a copper-adequate or a marginally copper-deficient diet for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was also given ad libitum. KCs were depleted by intravenous administration of gadolinium chloride (GdCl3) before and/or in the middle of the experimental period. Hepatic triglyceride accumulation was completely eliminated with KC depletion in CuMF consumption rats, which was associated with the normalization of elevated plasma monocyte chemoattractant protein-1 (MCP-1) and increased hepatic sterol regulatory element binding protein-1 expression. However, hepatic copper and iron content were not significantly affected by KC depletion. In addition, KC depletion reduced body weight and epididymal fat weight as well as adipocyte size. Plasma endotoxin and gut permeability were markedly increased in CuMF rats. Moreover, MCP-1 was robustly increased in the culture medium when isolated KCs from CuMF rats were treated with LPS. Our data suggest that KCs play a critical role in the development of hepatic steatosis induced by marginal-copper high-fructose diet.

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High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2015.08.025 ◽

2015 ◽

Vol 62 ◽

pp. 252-264 ◽

Cited By ~ 25

Author(s):

Constance S. Harrell ◽

Jillybeth Burgado ◽

Sean D. Kelly ◽

Zachary P. Johnson ◽

Gretchen N. Neigh

Keyword(s):

Male Rats ◽

High Fructose Diet ◽

High Fructose

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A high fructose diet impairs spatial memory in male rats

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2009.05.007 ◽

2009 ◽

Vol 92 (3) ◽

pp. 410-416 ◽

Cited By ~ 91

Author(s):

A.P. Ross ◽

T.J. Bartness ◽

J.G. Mielke ◽

M.B. Parent

Keyword(s):

Spatial Memory ◽

Male Rats ◽

High Fructose Diet ◽

High Fructose

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Sex modifies the consequences of extended fructose consumption on liver health, motor function, and physiological damage in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00046.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. R903-R911 ◽

Cited By ~ 8

Author(s):

Molly M. Hyer ◽

Samya K. Dyer ◽

Alix Kloster ◽

Anum Adrees ◽

Thomas Taetzsch ◽

...

Keyword(s):

Structural Changes ◽

Female Rats ◽

Male Rats ◽

Motor Deficits ◽

Male And Female ◽

Nonalcoholic Fatty Liver ◽

High Fructose Diet ◽

Male And Female Rats ◽

High Fructose ◽

Liver Health

Sex differences are evident in the presentation of metabolic symptoms. A shift of sex hormones that signal the onset of puberty combined with a poor diet consumed in adolescence is likely to have sex-specific, long-term impacts on adult physiology. Here, we expanded on existing literature to elucidate the sex-specific mechanisms driving physiological deficits following high fructose consumption. Male and female Wistar rats were fed a high-fructose (55%) diet beginning immediately postweaning for 10 wk. Female rats fed the high-fructose diet displayed elevated weight gain and extensive liver pathology consistent with markers of nonalcoholic fatty liver disease (NAFLD). Male rats fed the high-fructose diet exhibited increased circulating glucose along with moderate hepatic steatosis. Levels of cytokines and gene expression of inflammatory targets were not altered by fructose consumption in either sex. However, circulating levels of markers for liver health, including alanine transaminase and uric acid, and markers for epithelial cell death were altered by fructose consumption. From the alterations in these markers for liver health, along with elevated circulating triglycerides, it was evident that liver health had deteriorated significantly and that a number of factors were at play. Both adult fructose-fed male and female rats displayed motor deficits that correlated with aberrant structural changes at the neuromuscular junction; however, these deficits were exacerbated in males. These data indicate that consumption of a high-fructose diet beginning in adolescence leads to adult pathology that is modified by sex. Identification of these sex-specific changes has implications for treatment of clinical presentation of metabolic syndrome and related disorders.

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Effect of crude Moringa oleifera Lam. seed extract on the blood markers of metabolic syndrome in high-fructose diet-fed growing Sprague-Dawley rats

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0045 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

Masiline Mapfumo ◽

Busisani W. Lembede ◽

Ashwell R. Ndhlala ◽

Eliton Chivandi

Keyword(s):

Body Mass ◽

Moringa Oleifera ◽

Seed Extract ◽

Plasma Triglyceride ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

High Fructose Diet ◽

Sprague Dawley Rats ◽

High Fructose

AbstractBackgroundMoringa oleifera seed has anti-diabetic and anti-obesogenic properties. This study interrogated the effect of crude hydroethanolic M. oleifera seed extract on the blood markers of metabolic syndrome (MetS) in high-fructose diet fed growing Sprague-Dawley rats.MethodsSixty 21-day old female and male Sprague-Dawley rat pups were randomly allocated to and administered one of the following treatment regimens daily for twelve weeks: group I – plain drinking water (PW)+plain gelatine cube (PC), group II – 20% (w/v) fructose solution (FS)+PC, group III – FS+100 mg/kg body mass fenofibrate in gelatine cube (FN), group IV – FS+low dose (50 mg/kg body mass) of M. oleifera in gelatine cube (LMol) and group V – FS+high dose (500 mg/kg body mass) of M. oleifera in gelatine cube (HMol). The rats in each treatment regimen had ad libitum access to a standard rat chow. After the 12-week trial, the rats were subjected to an oral glucose tolerance test and then euthanised 48 h later. Blood was collected. Plasma triglyceride, cholesterol and insulin concentration were determined. HOMA-IR was then computed.ResultsThe high-fructose diet increased (p<0.05) plasma insulin concentration and HOMA-IR in female rats only. It increased plasma triglyceride concentration in both female and male rats and plasma cholesterol concentration in male rats only. The crude hydroethanolic M. oleifera seed extract prevented the high-fructose diet-induced metabolic derangements in male and female rats.ConclusionCrude hydroethanolic M. oleifera seed extract can potentially be used as a prophylactic intervention for diet-induced MetS in children.

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Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00076.2017 ◽

2017 ◽

Vol 313 (2) ◽

pp. E203-E212 ◽

Cited By ~ 23

Author(s):

Natsasi Chukijrungroat ◽

Tanaporn Khamphaya ◽

Jittima Weerachayaphorn ◽

Thaweesak Songserm ◽

Vitoon Saengsirisuwan

Keyword(s):

Sex Differences ◽

Protein Expression ◽

Fatty Liver ◽

Hepatic Steatosis ◽

Male Rats ◽

High Fat ◽

High Fructose Diet ◽

Ovx Rats ◽

High Fructose

The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis.

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