Spermidine and Voluntary Activity Exert Differential Effects on Sucrose- Compared with Fat-Induced Systemic Changes in Male Mice

ABSTRACT Background Excess dietary fat and sugar are linked to obesity and metabolic syndrome. Polyamines such as spermidine are implicated in fat accumulation and may support activity-induced weight loss. Objective This study tested interventional spermidine supplementation and voluntary activity against fat- and sucrose-induced systemic and gut microbiota changes. Methods A 3-factorial study design (3 × 2 × 2) was used to test the factors diet, activity, and spermidine. Male 6-wk-old C57BL/6N mice were fed a control diet (CD; carbohydrate:protein:fat, 70%:20%:10% of energy; 7% sucrose), a high-fat diet (HFD; carbohydrate:protein:fat, 20%:20%:60% of energy; 7% sucrose), or a high-sucrose diet (HSD; carbohydrate:protein:fat, 70%:20%:10% of energy; 35% sucrose). Diet groups were left untreated (+0) or had unlimited access to running wheels (+A) or were supplemented with 3 mM spermidine via drinking water (+S) or a combination of both (+A+S) for 30 wk (n = 7–10). Results In comparison to the CD, the HFD enhanced body weights (by 36%, P < 0.001), plasma lipids (cholesterol by 24%, P < 0.001; triglycerides by 27%, P = 0.004), and glucose concentrations (by 18%, P < 0.001), whereas the HSD increased weight by 13% (P < 0.001) and fasting glucose by 17% (P < 0.001) but did not increase plasma lipids. Microbiota taxonomic composition changed upon the HFD and HSD (both P < 0.001); however, only the HSD increased microbial diversity (P < 0.001) compared with the CD. Activity influenced microbiota composition (P < 0.01) and reduced glucose concentrations in HSD-fed (P = 0.021) and HFD-fed (P < 0.001) mice compared with nonactive mice. The combination of activity and spermidine affected energy intake (P-interaction = 0.037) and reduced body weights of HSD+A+S mice compared with HSD+0 mice (P = 0.024). Conclusions In male C57BL/6N mice, dietary sucrose and fat caused diverse metabolic and microbiota changes that were differentially susceptible to physical exercise. Spermidine has the potential to augment activity-induced beneficial effects, particularly for sucrose-induced obesity.

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Dietary supplementation with an extract of lycopene-rich tomatoes does not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

British Journal Of Nutrition ◽

10.1017/s0007114507210153 ◽

2007 ◽

Vol 97 (1) ◽

pp. 6-10 ◽

Cited By ~ 14

Author(s):

Hanne Frederiksen ◽

Salka E. Rasmussen ◽

Malene Schrøder ◽

Anette Bysted ◽

Jette Jakobsen ◽

...

Keyword(s):

Plasma Levels ◽

Intervention Studies ◽

Plasma Lipids ◽

Control Diet ◽

Dietary Supplementation ◽

Plant Oils ◽

Aortic Atherosclerosis ◽

Total Plasma ◽

Beneficial Effects ◽

Tomato Extract

Tomatoes are rich in lycopene and other carotenoids which have shown beneficial effects on CVD in epidemiological and intervention studies. In the present study the effect of an extract of lycopene-rich tomatoes, Lyc-O-Mato® on atherosclerosis was studied in Watanabe Heritable Hyperlipidemic rabbits. The rabbits were fed a control diet, a control diet supplemented with the tomato extract or a control diet supplemented with a mixture of plant oils for 16 weeks. Lycopene was detected only in plasma of rabbits receiving tomato extract. The tomato extract had no effect on cholesterol and triacylglycerol levels measured in total plasma, lipoprotein fractions and on aortic atherosclerosis evaluated biochemically and by microscopy. Oxidation of lipids in unfractionated plasma also was unaffected by the intake of tomato extract. In conclusion, the tomato extract increased plasma levels of lycopene in rabbits, but had no effect on hypercholesterolaemia, oxidation of plasma lipids or aortic atherosclerosis.

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Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients

Endocrinology ◽

10.1210/en.2015-1624 ◽

2016 ◽

Vol 157 (4) ◽

pp. 1421-1429 ◽

Cited By ~ 10

Author(s):

Amy E. Levenson ◽

Mary E. Haas ◽

Ji Miao ◽

Rebecca J. Brown ◽

Sarah D. de Ferranti ◽

...

Keyword(s):

Ldl Cholesterol ◽

Plasma Lipids ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Underlying Mechanism ◽

Male And Female ◽

Plasma Triglycerides ◽

Beneficial Effects ◽

Osmotic Pumps ◽

Reduced Body

Abstract Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5–23 y) with sc metreleptin injections (∼4.4 mg/d) for 4–6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r2 = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol.

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PSVI-11 The Effects of Medium Chain Fatty Acid Supplementation on Sow and Piglet Performance

Journal of Animal Science ◽

10.1093/jas/skab054.332 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 203-204

Author(s):

Analicia J Swanson ◽

Jorge Y Perez-Palencia ◽

Crystal L Levesque ◽

Amanda Hesse

Keyword(s):

Maternal Diet ◽

Control Diet ◽

Chain Fatty Acid ◽

Fatty Acid Supplementation ◽

Nursery Pigs ◽

Medium Chain ◽

Body Weights ◽

Feeding Program ◽

Nursery Pig ◽

Weaning Piglets

Abstract A total of 38 mixed parity sows were used from 28-d of gestation until weaning to determine the effects of medium chain fatty acids (MCFA) in sow and nursery pig diets on litter characteristics and growth performance. On 28-d of gestation, sows were blocked by parity and body weight (BW), and allotted to either a control diet (UNSUP) or a control diet plus 0.3% inclusion of DaaFit Plus (MCFA) fed during gestation and lactation. At weaning, piglets (n=432) were allocated in a 2x2 factorial based on maternal diet (UNSUP or MCFA) and post-weaning diet (UNSUPnurs or MCFAnurs) in a 3-phase nursery pig feeding program lasting 42 days. Individual piglets were weighed at birth, 7-d, at weaning and every 2 weeks post-weaning. A flu outbreak occurred during the latter part of gestation leading to high overall stillborn rate (11%). There was no impact of MCFA supplementation on sow performance (P>0.14). During the suckling period, MCFA fed to sows had no impact on piglet weights or ADG (P>0.82). In the nursey period, overall gain (0.112±0.02 kg) was low in the first two weeks possibly due to health challenges. Supplementation of MCFA to sows or nursery pigs had no impact on body weights during the nursery period (P>0.32); however, absolute differences between groups increased with week [wean, 0.10kg; wk 2, 0.14kg; wk 4, 0.71kg; wk 6, 0.83kg) to the advantage of MCFA fed pigs. Pigs from MCFA fed sows had greater feed intake (P< 0.02) from 14 to 28-d and decreased gain:feed (P < 0.04) from 28 to 42-d compared to pigs from UNSUP sows. Overall, sow and nurser-y pigs fed MCFA had numerically greater 42-d BW, ADG, and ADFI. In conclusion, despite health challenges, supplementation with MCFA in gestation, lactation or in the nursery period improved piglet performance.

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Navy Bean Supplementation in Established High-Fat Diet-Induced Obesity Attenuates the Severity of the Obese Inflammatory Phenotype

Nutrients ◽

10.3390/nu13030757 ◽

2021 ◽

Vol 13 (3) ◽

pp. 757

Author(s):

Jennifer M. Monk ◽

Wenqing Wu ◽

Dion Lepp ◽

K. Peter Pauls ◽

Lindsay E. Robinson ◽

...

Keyword(s):

Weight Loss ◽

Control Diet ◽

Intestinal Health ◽

High Fat ◽

Navy Bean ◽

Fecal Microbiome ◽

Reduced Body ◽

Inflammatory Phenotype ◽

Obesogenic Diet ◽

Obese Phenotype

Cooked common beans (Phaseolus vulgaris) improve intestinal health in lean mice and attenuate intestinal dysbiosis and inflammation when consumed concurrent with obesity development. We determined the effects of a high-fat (HF) bean supplemented diet in mice with established obesity (induced by 12 weeks of HF diet (60% fat as kcal)) compared to obese mice consuming a HF or low-fat (LF) weight loss control diet. Obese C57BL/6 male mice remained consuming HF for eight weeks or were randomly switched from HF to an isocaloric HF with 15.7% cooked navy bean powder diet (HFàHFB) or LF (11% fat as kcal; HFàLF) (n = 12/group). HFàHFB improved the obese phenotype, including (i) fecal microbiome (increased Prevotella, Akkermansia muciniphila, and short-chain fatty acid levels), (ii) intestinal health (increased ZO-1, claudin-2, Muc2, Relmβ, and Reg3γ expression), and (iii) reduced adipose tissue (AT) inflammatory proteins (NFκBp65, STAT3, IL-6, MCP-1, and MIP-1α), versus HF (p < 0.05). Conversely, HFàLF reduced body weight and circulating hormones (leptin, resistin, and PAI-1) versus HF and HFàHFB (p < 0.05); however, AT inflammation and intestinal health markers were not improved to the same degree as HFàHFB (p < 0.05). Despite remaining on a HF obesogenic diet, introducing beans in established obesity improved the obese phenotype (intestinal health and adipose inflammation) more substantially than weight loss alone.

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Insulin treatment improves liver histopathology and decreases expression of inflammatory and fibrogenic genes in a hyperglycemic, dyslipidemic hamster model of NAFLD

Journal of Translational Medicine ◽

10.1186/s12967-021-02729-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Victoria Svop Jensen ◽

Christian Fledelius ◽

Christina Zachodnik ◽

Jesper Damgaard ◽

Helle Nygaard ◽

...

Keyword(s):

Cell Activation ◽

Insulin Treatment ◽

Stellate Cell ◽

Control Diet ◽

Diabetic Patients ◽

Liver Pathology ◽

Hamster Model ◽

Alcoholic Fatty Liver ◽

Beneficial Effects ◽

Liver Histopathology

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent comorbidities in patients with Type 2 diabetes. While many of these patients eventually will need treatment with insulin, little is known about the effects of insulin treatment on histopathological parameters and hepatic gene expression in diabetic patients with co-existing NAFLD and NASH. To investigate this further, we evaluated the effects of insulin treatment in NASH diet-fed hamsters with streptozotocin (STZ) -induced hyperglycemia. Methods Forty male Syrian hamsters were randomized into four groups (n = 10/group) receiving either a NASH-inducing (high fat, fructose and cholesterol) or control diet (CTRL) for four weeks, after which they were treated with STZ or sham-injected and from week five treated with either vehicle (CTRL, NASH, NASH-STZ) or human insulin (NASH-STZ-HI) for four weeks by continuous s.c. infusion via osmotic minipumps. Results NASH-STZ hamsters displayed pronounced hyperglycemia, dyslipidemia and more severe liver pathology compared to both CTRL and NASH groups. Insulin treatment attenuated dyslipidemia in NASH-STZ-HI hamsters and liver pathology was considerably improved compared to the NASH-STZ group, with prevention/reversal of hepatic steatosis, hepatic inflammation and stellate cell activation. In addition, expression of inflammatory and fibrotic genes was decreased compared to the NASH-STZ group. Conclusions These results suggest that hyperglycemia is important for development of inflammation and profibrotic processes in the liver, and that insulin administration has beneficial effects on liver pathology and expression of genes related to inflammation and fibrosis in a hyperglycemic, dyslipidemic hamster model of NAFLD.

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Mice with Deficiency of G Protein γ3 Are Lean and Have Seizures

Molecular and Cellular Biology ◽

10.1128/mcb.24.17.7758-7768.2004 ◽

2004 ◽

Vol 24 (17) ◽

pp. 7758-7768 ◽

Cited By ~ 54

Author(s):

William F. Schwindinger ◽

Kathryn E. Giger ◽

Kelly S. Betz ◽

Anna M. Stauffer ◽

Elaine M. Sunderlin ◽

...

Keyword(s):

Signaling Pathways ◽

G Protein ◽

Gene Targeting ◽

Wild Type ◽

Phenotypic Changes ◽

Reduced Body ◽

Γ Subunit ◽

Body Weights ◽

The Brain ◽

Increased Susceptibility

ABSTRACT Emerging evidence suggests that the γ subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve γ subtypes, γ3 is abundantly and widely expressed in the brain. To identify specific functions and associations for γ3, a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3 −/−). Confirming the efficacy and specificity of gene targeting, Gng3 −/− mice show no detectable expression of the Gng3 gene, but expression of the divergently transcribed Bscl2 gene is not affected. Suggesting unique roles for γ3 in the brain, Gng3 −/− mice display increased susceptibility to seizures, reduced body weights, and decreased adiposity compared to their wild-type littermates. Predicting possible associations for γ3, these phenotypic changes are associated with significant reductions in β2 and αi3 subunit levels in certain regions of the brain. The finding that the Gng3 −/− mice and the previously reported Gng7 −/− mice display distinct phenotypes and different αβγ subunit associations supports the notion that even closely related γ subtypes, such as γ3 and γ7, perform unique functions in the context of the organism.

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Growth and zinc homeostasis in the severely Zn-deficient rat

British Journal Of Nutrition ◽

10.1079/bjn19840122 ◽

1984 ◽

Vol 52 (3) ◽

pp. 545-560 ◽

Cited By ~ 86

Author(s):

R. Giugliano ◽

D. J. Millward

Keyword(s):

Body Weight ◽

Growth Rates ◽

Control Diet ◽

Rate Of Change ◽

Zinc Homeostasis ◽

Whole Body ◽

Zn Deficiency ◽

Control Groups ◽

Body Weights ◽

Cyclic Changes

1. Male weanling rats were fed on diets either adequate (55 mg/kg), or severely deficient (0.4 mg/kg) in zinc, either ad lib. or in restricted amounts in four experiments. Measurements were made of growth rates and Zn contents of muscle and several individual tissues.2. Zn-deficient rats exhibited the expected symptoms of deficiency including growth retardation, cyclic changes in food intake and body-weight.3. Zn deficiency specifically reduced whole body and muscle growth rates as indicated by the fact that (a) growth rates were lower in ad lib.-fed Zn-deficient rats compared with rats pair-fed on the control diet in two experiments, (b) Zn supplementation increased body-weights of Zn-deficient rats given a restricted amount of diet at a level at which they maintained weight if unsupplemented, (c) Zn supplementation maintained body-weights of Zn-deficient rats fed a restricted amount of diet at a level at which they lost weight if unsupplemented (d) since the ratio, muscle mass:body-weight was lower in the Zn-deficient rats than in the pair-fed control groups, the reduction in muscle mass was greater than the reduction in body-weight.4. Zn concentrations were maintained in muscle, spleen and thymus, reduced in comparison to some but not all control groups in liver, kidney, testis and intestine, and markedly reduced in plasma and bone. In plasma, Zn concentrations varied inversely with the rate of change of body-weight during the cyclic changes in body-weight.5. Calculation of the total Zn in the tissues examined showed a marked increase in muscle Zn with a similar loss from bone, indicating that Zn can be redistributed from bone to allow the growth of other tissues.6. The magnitude of the increase in muscle Zn in the severely Zn-deficient rat, together with the magnitude of the total losses of muscle tissue during the catabolic phases of the cycling, indicate that in the Zn-deficient rat Zn may be highly conserved in catabolic states.

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Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Bromodichloromethane (BDCM) in Rats

International Journal of Toxicology ◽

10.1080/10915810252866097 ◽

2002 ◽

Vol 21 (2) ◽

pp. 115-146 ◽

Cited By ~ 18

Author(s):

M. S. Christian ◽

R. G. York ◽

A. M. Hoberman ◽

L. C. Fisher ◽

W. Ray Brown

Keyword(s):

Drinking Water ◽

Reproductive Toxicity ◽

Clinical Signs ◽

Sperm Parameters ◽

Feed Consumption ◽

Exposure Level ◽

Organ Weights ◽

Reduced Body ◽

Body Weights ◽

Adult Exposure

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50, 150, and 450 ppm (0,4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 μg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling F1 and F2 pups/sex/litter], histopathology [10/sex, 0-and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling F1 and F2 pups/sex/litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0-and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (F1 adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more F1 rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.

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Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α

British Journal Of Nutrition ◽

10.1017/s0007114507207627 ◽

2007 ◽

Vol 97 (2) ◽

pp. 389-398 ◽

Cited By ~ 131

Author(s):

Patricia Pérez-Matute ◽

Nerea Pérez-Echarri ◽

J. Alfredo Martínez ◽

Amelia Marti ◽

María J. Moreno-Aliaga

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Body Weight Gain ◽

Control Diet ◽

Cafeteria Diet ◽

High Fat ◽

Beneficial Effects

n-3 PUFA have shown potential anti-obesity and insulin-sensitising properties. However, the mechanisms involved are not clearly established. The aim of the present study was to assess the effects of EPA administration, one of the n-3 PUFA, on body-weight gain and adiposity in rats fed on a standard or a high-fat (cafeteria) diet. The actions on white adipose tissue lipolysis, apoptosis and on several genes related to obesity and insulin resistance were also studied. Control and cafeteria-induced overweight male Wistar rats were assigned into two subgroups, one of them daily received EPA ethyl ester (1 g/kg) for 5 weeks by oral administration. The high-fat diet induced a very significant increase in both body weight and fat mass. Rats fed with the cafeteria diet and orally treated with EPA showed a marginally lower body-weight gain (P = 0·09), a decrease in food intake (P < 0·01) and an increase in leptin production (P < 0·05). EPA administration reduced retroperitoneal adipose tissue weight (P < 0·05) which could be secondary to the inhibition of the adipogenic transcription factor PPARγ gene expression (P < 0·001), and also to the increase in apoptosis (P < 0·05) found in rats fed with a control diet. TNFα gene expression was significantly increased (P < 0·05) by the cafeteria diet, while EPA treatment was able to prevent (P < 0·01) the rise in this inflammatory cytokine. Adiposity-corrected adiponectin plasma levels were increased by EPA. These actions on both TNFα and adiponectin could explain the beneficial effects of EPA on insulin resistance induced by the cafeteria diet.

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Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

10.1101/2020.12.10.420695 ◽

2020 ◽

Author(s):

Benjamin Ng ◽

Anissa A. Widjaja ◽

Sivakumar Viswanathan ◽

Jinrui Dong ◽

Sonia P. Chothani ◽

...

Keyword(s):

Knockout Mice ◽

Lung Fibroblasts ◽

Loss Of Function ◽

Wild Type ◽

Reduced Body ◽

Body Weights ◽

Show Evidence ◽

Similarities And Differences ◽

The Impact

AbstractGenetic loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and craniosynostosis. The impact of genetic LOF in IL11 has not been characterized. We generated IL11-knockout (Il11-/-) mice, which are born in normal Mendelian ratios, have normal hematological profiles and are protected from bleomycin-induced lung fibro-inflammation. Noticeably, baseline IL6 levels in the lungs of Il11-/- mice are lower than those of wild-type mice and are not induced by bleomycin damage, placing IL11 upstream of IL6. Lung fibroblasts from Il11-/- mice are resistant to pro-fibrotic stimulation and show evidence of reduced autocrine IL11 activity. Il11-/- female mice are infertile. Unlike Il11ra1-/- mice, Il11-/- mice do not have a craniosynostosis-like phenotype and exhibit mildly reduced body weights. These data highlight similarities and differences between LOF in IL11 or IL11RA while establishing further the role of IL11 signaling in fibrosis and stromal inflammation.

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