Switching Adolescent High-Fat Diet to Adult Control Diet Restores Neurocognitive Alterations

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

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Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mito-Phagy in Female Rat Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms22147551 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7551

Author(s):

Sven H. Rouschop ◽

Samantha J. Snow ◽

Urmila P. Kodavanti ◽

Marie-José Drittij ◽

Lou M. Maas ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

High Fat Diet ◽

Control Diet ◽

Ozone Exposure ◽

Female Rat ◽

Induced Responses ◽

High Fat ◽

Molecular Control ◽

Rat Offspring ◽

Oxidant Status

Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.

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Flavonoids from Mulberry Leaves Alleviate Lipid Dysmetabolism in High Fat Diet-Fed Mice: Involvement of Gut Microbiota

Microorganisms ◽

10.3390/microorganisms8060860 ◽

2020 ◽

Vol 8 (6) ◽

pp. 860 ◽

Cited By ~ 1

Author(s):

Yinzhao Zhong ◽

Bo Song ◽

Changbing Zheng ◽

Shiyu Zhang ◽

Zhaoming Yan ◽

...

Keyword(s):

Acetic Acid ◽

Lipid Metabolism ◽

Gut Microbiota ◽

High Fat Diet ◽

Control Diet ◽

Liver Steatosis ◽

High Fat ◽

Acetic Acid Production ◽

Mulberry Leaves ◽

Brown Adipose

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for six weeks. FML administration improved lipid accumulation, alleviated liver steatosis and the whitening of brown adipose tissue, and improved gut microbiota composition in HFD-fed mice. Microbiota transplantation from FML-treated mice alleviated HFD-induced lipid metabolic disorders. Moreover, FML administration restored the production of acetic acid in HFD-fed mice. Correlation analysis identified a significant correlation between the relative abundances of Bacteroidetes and the production of acetic acid, and between the production of acetic acid and the weight of selected adipose tissues. Overall, our results demonstrated that in HFD-fed mice, the lipid metabolism improvement induced by FML administration might be mediated by gut microbiota, especially Bacteroidetes-triggered acetic acid production.

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Effect of selective expression of dominant-negative PPARγ in pro-opiomelanocortin neurons on the control of energy balance

Physiological Genomics ◽

10.1152/physiolgenomics.00032.2016 ◽

2016 ◽

Vol 48 (7) ◽

pp. 491-501 ◽

Cited By ~ 9

Author(s):

Madeliene Stump ◽

Deng-Fu Guo ◽

Ko-Ting Lu ◽

Masashi Mukohda ◽

Xuebo Liu ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Energy Balance ◽

High Fat Diet ◽

Control Diet ◽

Cre Recombinase ◽

Dominant Negative ◽

High Fat ◽

Pparγ Agonist ◽

The Brain

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.

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Abstract 58: Angiotensin-(1-7) Mas Receptors In The Arcuate Nucleus Of The Hypothalamus Protect Against High Fat Diet-induced Insulin Resistance In Female Mice

Hypertension ◽

10.1161/hyp.78.suppl_1.58 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Darren Mehay ◽

Sarah Bingaman ◽

Yuval Silberman ◽

Amy Arnold

Keyword(s):

Body Composition ◽

Insulin Sensitivity ◽

Energy Balance ◽

Glucose Tolerance ◽

High Fat Diet ◽

Metabolic Regulation ◽

Arcuate Nucleus ◽

Control Diet ◽

High Fat ◽

Metabolic Outcomes

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that improves insulin sensitivity, glucose tolerance, and energy balance in obese rodents. Our recent findings suggest that Ang-(1-7) activates mas receptors (MasR) in the arcuate nucleus of the hypothalamus (ARC), a brain region critical to control of energy balance and glucose homeostasis, to induce these positive metabolic effects. The distribution of MasR in the ARC and their role in metabolic regulation, however, is unknown. We hypothesized: (1) MasR are expressed in the ARC; and (2) deletion of ARC MasR leads to worsened metabolic outcomes following high fat diet (HFD). To test this, male and female C57Bl/6J mice were fed a 60% HFD or matched control diet ad libitum for 12 weeks. RNAscope in situ hybridization was performed on coronal ARC sections in rostral-middle-caudal regions to determine percentage of MasR positive neurons (n=5/group). In a second experiment, we assessed body composition and insulin and glucose tolerance in transgenic mice with deletion of MasR in ARC neurons (MasR-flox with AAV5-hsyn-GFP-Cre). RNAscope revealed a wide distribution on MasR-positive cells throughout the rostral to caudal extent of the ARC. The average percentage of MasR positive neurons was increased in females versus males, with HFD tending to increase MasR expression in both sexes (control diet male: 11±2; control diet female: 17±3; HFD male: 15±5; HFD female: 24±2; p sex : 0.030; p diet : 0.066; p int : 0.615; two-way ANOVA). Deletion of MasR in ARC neurons worsened insulin sensitivity in HFD but not control diet females (area under the curve for change in glucose from baseline: -1989±1359 HFD control virus vs. 2530±1762 HFD Cre virus; p=0.016), while fasting glucose, glucose tolerance, and body composition did not change. There was no effect of ARC MasR deletion on metabolic outcomes in control diet or HFD male mice. These findings suggest females have more MasR positive neurons in the ARC compared to males, which may be a sex-specific protective mechanism for glucose homeostasis. While further studies are needed to explore the role of ARC MasR in metabolic regulation, these findings support targeting Ang-(1-7) as an innovative strategy in obesity.

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Abstract MP05: The Mechanism Of The Pvat Pro-inflammatory Micro-environment Formation During The Development Of High Fat Diet-induced Hypertension

Hypertension ◽

10.1161/hyp.78.suppl_1.mp05 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Yining Jin ◽

Omar Kana ◽

Ramya Kumar ◽

Rance Nault ◽

Hannah Garver ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

High Fat Diet ◽

Cell Activation ◽

Control Diet ◽

Rna Seq ◽

High Fat ◽

Induced Hypertension ◽

Th17 Differentiation

There is considerable evidence for a causative role for T cells in hypertension, including studies with immunosuppressive drugs and T cell-deficient models. Our previous studies showed that soluble mediators from mesenteric perivascular adipose tissue (mPVAT) modulate T cell function. Specifically, conditioned media from mPVAT (mPVAT-CM) from Dahl S rats on a high fat diet (HFD) promoted expression of the pro-inflammatory cytokines, IFNg, IL-17a and GM-CSF, by activated T cells. Furthermore, the Dahl S rats on HFD will later develop hypertension. Hypothesis: mPVAT is stimulated to produce immunomodulatory mediators that promotes Th1/17 differentiation preceding the development of HFD-induced hypertension. We conducted bulk RNA-seq on activated splenocytes cultured in mPVAT-CM from Dahl S rats on either control or HFD for 10 weeks. In accordance with our previous studies, PVAT-CM from HFD-fed rats significantly upregulated many genes associated with IFNg/IL-17 induction, including Mpeg1, Lyz2 and Tnfsf4 (5.0±1.78, 3.70±0.53 and 1.78±0.42 fold over Control diet, respectively). In contrast, Th2/Treg-associated genes, such as Ctla2a (-0.27±0.02) and Ccr4 (-0.41±0.03) were downregulated. We also performed single cell (sc) RNA-seq on the PVAT stromal vascular fraction (SVF) and found that acute inflammatory genes were enriched in the HFD group. Together with the bulk RNA-seq on mPVAT, these data strongly suggest that the pro-inflammatory mPVAT micro-environment may promote Th1/Th17 differentiation. To identify mediators in PVAT-CM that may induce Th1/Th17 differentiation, we compared the bulk RNA-seq on splenocytes cultured in PVAT-CM with bulk RNA-seq conducted on the whole mPVAT itself. We found that a T cell co-stimulatory receptor DPP4 (CD26), which is closely associated with T cell activation was significantly increased in mPVAT from HFD-fed rats (33.4±2.3 HFD vs. 15.3±1.8 Control diet). We also observed an increase in DPP4 global expression from mPVAT SVF in HFD-fed rats, as determined by scRNA-seq. Conclusion: The data suggest that HFD promotes the IFNg and IL-17a pathways in PVAT, which precedes hypertension in Dahl S rats and correlates with an increase in expression of DPP-4, a gene that promotes T cell activation. (NIH P01 HL070687).

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Effects of a high-fat-diet supplemented with probiotics and ω3-fatty acids on appetite regulatory neuropeptides and neurotransmitters in a pig model

Beneficial Microbes ◽

10.3920/bm2019.0197 ◽

2020 ◽

Vol 11 (4) ◽

pp. 347-359

Author(s):

D. Valent ◽

L. Arroyo ◽

E. Fàbrega ◽

M. Font-i-Furnols ◽

M. Rodríguez-Palmero ◽

...

Keyword(s):

Fatty Acids ◽

Animal Model ◽

Weight Gain ◽

Food Intake ◽

High Fat Diet ◽

Control Diet ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

High Fat ◽

Brain Functions

The pig is a valuable animal model to study obesity in humans due to the physiological similarity between humans and pigs in terms of digestive and associated metabolic processes. The dietary use of vegetal protein, probiotics and omega-3 fatty acids is recommended to control weight gain and to fight obesity-associated metabolic disorders. Likewise, there are recent reports on their beneficial effects on brain functions. The hypothalamus is the central part of the brain that regulates food intake by means of the production of food intake-regulatory hypothalamic neuropeptides, as neuropeptide Y (NPY), orexin A and pro-opiomelanocortin (POMC), and neurotransmitters, such as dopamine and serotonin. Other mesolimbic areas, such as the hippocampus, are also involved in the control of food intake. In this study, the effect of a high fat diet (HFD) alone or supplemented with these additives on brain neuropeptides and neurotransmitters was assessed in forty-three young pigs fed for 10 weeks with a control diet (T1), a high fat diet (HFD, T2), and HFD with vegetal protein supplemented with Bifidobacterium breve CECT8242 alone (T3) or in combination with omega-3 fatty acids (T4). A HFD provoked changes in regulatory neuropeptides and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and alterations mostly in the dopaminergic system in the ventral hippocampus. Supplementation of the HFD with B. breve CECT8242, especially in combination with omega-3 fatty acids, was able to partially reverse the effects of HFD. Correlations between productive and neurochemical parameters supported these findings. These results confirm that pigs are an appropriate animal model alternative to rodents for the study of the effects of HFD on weight gain and obesity. Furthermore, they indicate the potential benefits of probiotics and omega-3 fatty acids on brain function.

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Effects of a Mixed Limosilactobacillus fermentum Formulation with Claimed Probiotic Properties on Cardiometabolic Variables, Biomarkers of Inflammation and Oxidative Stress in Male Rats Fed a High-Fat Diet

Foods ◽

10.3390/foods10092202 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2202

Author(s):

Micaelle Oliveira de Luna Freire ◽

Luciana Caroline Paulino do Nascimento ◽

Kataryne Árabe Rimá de Oliveira ◽

Alisson Macário de Oliveira ◽

Thiago Henrique Napoleão ◽

...

Keyword(s):

Oxidative Stress ◽

High Fat Diet ◽

Control Diet ◽

Male Rats ◽

Control Group ◽

Low Grade ◽

Probiotic Properties ◽

High Fat ◽

Low Grade Inflammation ◽

And Oxidative Stress

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.

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The Role of Perivascular Adipose Tissue in Early Changes in Arterial Function during High-Fat Diet and Its Combination with High-Fructose Intake in Rats

Biomedicines ◽

10.3390/biomedicines9111552 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1552

Author(s):

Jozef Torok ◽

Anna Zemancikova ◽

Zuzana Valaskova ◽

Peter Balis

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Control Diet ◽

Sympathetic Nerves ◽

High Fat ◽

Perivascular Adipose Tissue ◽

Fructose Intake ◽

High Fructose ◽

Wistar Kyoto ◽

Isolated Arteries

The aim of the current study was to evaluate the influence of a high-fat diet and its combination with high-fructose intake on young normotensive rats, with focus on the modulatory effect of perivascular adipose tissue (PVAT) on the reactivity of isolated arteries. Six-week-old Wistar–Kyoto rats were treated for 8 weeks with a control diet (10% fat), a high-fat diet (HFD; 45% fat), or a combination of the HFD with a 10% solution of fructose. Contractile and relaxant responses of isolated rat arteries, with preserved and removed PVAT for selected vasoactive stimuli, were recorded isometrically by a force displacement transducer. The results demonstrated that, in young rats, eight weeks of the HFD might lead to body fat accumulation and early excitation of the cardiovascular sympathetic nervous system, as shown by increased heart rate and enhanced arterial contractile responses induced by endogenous noradrenaline released from perivascular sympathetic nerves. The addition of high-fructose intake deteriorated this state by impairment of arterial relaxation and resulted in mild elevation of systolic blood pressure; however, the increase in arterial neurogenic contractions was not detected. The diet-induced alterations in isolated arteries were observed only in the presence of PVAT, indicating that this structure is important in initiation of early vascular changes during the development of metabolic syndrome.

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Hypocholesterolaemic effect of whole-grain highland hull-less barley in rats fed a high-fat diet

British Journal Of Nutrition ◽

10.1017/s0007114518000831 ◽

2018 ◽

Vol 119 (10) ◽

pp. 1102-1110 ◽

Cited By ~ 8

Author(s):

Xuejuan Xia ◽

Guannan Li ◽

Jiaxin Song ◽

Jiong Zheng ◽

Jianquan Kan

Keyword(s):

Bile Acid ◽

High Fat Diet ◽

Control Diet ◽

Ldl Receptor ◽

Acid Synthesis ◽

Farnesoid X Receptor ◽

High Dose ◽

Whole Grain ◽

Sprague Dawley ◽

High Fat

AbstractWhole-grain highland hull-less barley (WHLB) contains high amounts of bioactive compounds that potentially exhibit cholesterol-lowering effects. This study investigated the hypocholesterolaemic effect of WHLB. A total of seventy-two male Sprague–Dawley rats were divided into four groups and were fed with the normal control diet, high-fat diet (HFD) and HFD containing low or high dose (10 or 48·95 %) of WHLB. High dose of WHLB significantly decreased the organ indexes of liver and abdominal fat and lipid levels of plasma and liver in HFD rats. The lipid regulation effect of WHLB, which was reconfirmed through hepatocyte morphologic observation, was accompanied by a large excretion of bile acids in the small intestinal contents and the faeces. Real-time PCR analyses, which were further reconfirmed through Western blot analyses, revealed that a high dose of WHLB significantly enhanced the hepatic expressions of AMP-activated protein kinase α, cholesterol 7α-hydroxylase, LDL receptor, liver X receptor, and PPARα and decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It also enhanced the ileal expression of farnesoid X receptor and resulted in the decrease of expression of apical sodium-dependent bile acid transporter. WHLB exhibited hypocholesterolaemic effects mainly by inhibiting cholesterol synthesis, cholesterol accumulation in peripheral tissue, and bile acid reabsorption and by stimulating bile acid synthesis.

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