Su1779 VIP Knockout Mice are Resistant to a Western Diet-Induced Body Weight and Fat Accumulation

IntroductionExercise training has been shown to be the most effective strategy to combat obesity and non-alcoholic fatty liver disease. However, exercise promotes loss of adipose tissue mass and improves obesity-related hepatic steatosis through mechanisms that remain obscure.Research design and methodsTo study the role of interleukin-6 (IL-6) in high-fat diet (HFD)-induced adiposity and hepatic steatosis during treadmill running, IL-6 knockout (IL-6 KO) mice and wild-type (WT) mice were randomly divided into lean, obese (fed a HFD) and trained obese groups (fed a HFD and exercise trained).ResultsAfter 20 weeks of HFD feeding and 8 weeks of treadmill running, we found that exercise obviously reduced HFD-induced body weight gain, inhibited visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) expansion and almost completely reversed obesity-related intrahepatic fat accumulation in WT mice. However, IL-6 knockout (IL-6 KO) mice are refractory to the benefits of treadmill training on body weight, VAT and SAT mass elevation, and hepatic steatosis. Moreover, a panel of lipolytic-related and thermogenic-related genes, including ATGL, HSL and PGC-1α, was upregulated in the VAT and SAT of WT mice that received exercise training compared with untrained mice, which was not observed in IL-6 KO mice. In addition, exercise training resulted in a significant inhibition of hepatic peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in WT mice, and these effects were not noted in IL-6 KO mice.ConclusionThese results revealed that IL-6 is involved in the prevention of obesity and hepatic fat accumulation during exercise training. The mechanisms underlying these antiobesity effects may be associated with enhanced lipolysis and thermogenesis in white adipose tissue. The improvement in hepatic steatosis by exercise training may benefit from the marked inhibition of PPAR-γ expression by IL-6.

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Effects of Preventive Acupuncture and Moxibustion on Fat Accumulation, Blood Lipid, and UterusE2of Menopause Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/621975 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Shi-Peng Zhu ◽

Yu-wei He ◽

Huan Chen ◽

Zhi-Fang Sun ◽

Na Ding ◽

...

Keyword(s):

Growth Rate ◽

Body Weight ◽

Density Lipoprotein ◽

Blood Lipid ◽

Control Group ◽

Young Control ◽

Fat Accumulation ◽

Acupuncture And Moxibustion ◽

Weight Growth ◽

Sd Rats

Objective. To observe the effect of preventive acupuncture and moxibustion on blood lipid of menopause rats.Methods. Seventy 10-month-old SD rats with estrous cycle disorders were divided into three control groups and four treatment groups (n=10/group) and another ten 3.5-month-old female SD rats were chosen as young control group. Preventive acupuncture and moxibustion were applied at Guanyuan (CV 4). Body weight growth rate has been recorded. Plasma total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels and uterusE2level were measured.Results. Compared to young control group, plasma TC and LDL increased and uterusE2reduced significantly in 12-month-old control group. Compared to 12-month-old control group, plasma TC and LDL level and body weight growth rate decreased while HDL level increased remarkably in preventive acupuncture 12-month-old group. Compared to 14-month-old control group, plasma TC level and body weight growth rate decreased remarkably in preventive moxibustion 14-month-old group.Conclusions. Preventive acupuncture and moxibustion can significantly decrease the plasma TG and LDL, increase the plasma HDL, and prevent fat accumulation. Our finding suggests that preventive acupuncture and moxibustion have beneficial effects on blood lipid. Different treatment effects were found between preventive acupuncture and preventive moxibustion.

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PP108-SUN WEIGHT CYCLING IS ASSOCIATED WITH BODY WEIGHT EXCESS AND ABDOMINAL FAT ACCUMULATION: A CROSS-SECTIONAL STUDY

Clinical Nutrition Supplements ◽

10.1016/s1744-1161(11)70162-4 ◽

2011 ◽

Vol 6 (1) ◽

pp. 65

Author(s):

E. Cereda ◽

A.E. Malavazos ◽

R. Caccialanza ◽

M. Rondanelli ◽

G. Fatati ◽

...

Keyword(s):

Body Weight ◽

Cross Sectional Study ◽

Abdominal Fat ◽

Weight Cycling ◽

Sectional Study ◽

Cross Sectional ◽

Fat Accumulation ◽

Weight Excess

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Western diet feeding influences gut microbiota profiles in apoE knockout mice

Lipids in Health and Disease ◽

10.1186/s12944-018-0811-8 ◽

2018 ◽

Vol 17 (1) ◽

Cited By ~ 23

Author(s):

Baoning Liu ◽

Yali Zhang ◽

Rong Wang ◽

Yingfeng An ◽

Weiman Gao ◽

...

Keyword(s):

Gut Microbiota ◽

Knockout Mice ◽

Western Diet ◽

Apoe Knockout Mice

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Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.2.r563 ◽

1997 ◽

Vol 272 (2) ◽

pp. R563-R569 ◽

Cited By ~ 19

Author(s):

L. R. Leon ◽

W. Kozak ◽

J. Peschon ◽

M. J. Kluger

Keyword(s):

Body Weight ◽

Food Intake ◽

Motor Activity ◽

Knockout Mice ◽

Low Dose ◽

Late Phase ◽

High Dose ◽

Wild Type ◽

Inflammatory Stimuli ◽

Necrosis Factor

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

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A Defect in Interleukin-10 Leads to Enhanced Malarial Disease in Plasmodium chabaudi chabaudi Infection in Mice

Infection and Immunity ◽

10.1128/iai.67.9.4435-4442.1999 ◽

1999 ◽

Vol 67 (9) ◽

pp. 4435-4442 ◽

Cited By ~ 166

Author(s):

Ching Li ◽

Inés Corraliza ◽

Jean Langhorne

Keyword(s):

Body Weight ◽

Knockout Mice ◽

Interleukin 10 ◽

Plasmodium Chabaudi ◽

Double Knockout ◽

Direct Stimulation ◽

Necrosis Factor Alpha ◽

Glucose Levels ◽

Tnf Α ◽

Ifn Γ

ABSTRACT Infection of interleukin-10 (IL-10)-nonexpressing (IL-10−/−) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10−/−mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10−/− mice produced more gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-γ in IL-10−/− mice by the injection of anti-IFN-γ antibodies or by the generation of IL-10−/− IFN-γ receptor−/− double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-γ-independent pathways may be responsible for these pathological features of P. chabaudimalaria and may be due to direct stimulation of TNF-α by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-γ or TNF-α produced.

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Susceptibility to diet induced obesity at thermoneutral conditions is independent of UCP1

10.1101/2021.06.30.450595 ◽

2021 ◽

Author(s):

Sebastian Dieckmann ◽

Akim Strohmeyer ◽

Monja Willershaeuser ◽

Stefanie Maurer ◽

Wolfgang Wurst ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Energy Expenditure ◽

Knockout Mice ◽

Body Weight Gain ◽

Uncoupling Protein ◽

Exon 2 ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Knockout Model

Objective Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of Exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. Methods UCP1 knockout and wildtype mice were housed at 30°C and fed a control diet for 4-weeks followed by 8-weeks of high-fat diet. Body weight and food intake were monitored continuously over the course of the study and indirect calorimetry was used to determine energy expenditure during both feeding periods. Results Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake and energy expenditure were not affected by deletion of UCP1 gene function during both feeding periods. Conclusion Conclusively, we show that UCP1 does not protect against diet-induced obesity at thermoneutrality. Further we introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages.

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The depot-specific and essential roles of CBP/p300 in regulating adipose plasticity

Journal of Endocrinology ◽

10.1530/joe-18-0361 ◽

2019 ◽

Vol 240 (2) ◽

pp. 257-269 ◽

Cited By ~ 2

Author(s):

Maria Namwanje ◽

Longhua Liu ◽

Michelle Chan ◽

Nikki Aaron ◽

Michael J Kraakman ◽

...

Keyword(s):

Body Weight ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Knockout Mice ◽

Metabolic Disorders ◽

Physiological Effects ◽

Double Knockout ◽

Adipose Tissues ◽

Diet Induced Obesity ◽

Specific Deletion

Fat remodeling has been extensively explored through protein deacetylation, but not yet acetylation, as a viable therapeutic approach in the management of obesity and related metabolic disorders. Here, we investigated the functions of key acetyltransferases CBP/p300 in adipose remodeling and their physiological effects by generating adipose-specific deletion of CBP (Cbp-AKO), p300 (p300-AKO) and double-knockout (Cbp/p300-AKO) models. We demonstrated that Cbp-AKO exhibited marked brown remodeling of inguinal WAT (iWAT) but not epididymal WAT (eWAT) after cold exposure and that this pattern was exaggerated in diet-induced obesity (DIO). Despite this striking browning phenotype, loss of Cbp was insufficient to impact body weight or glucose tolerance. In contrast, ablation of p300 in adipose tissues had minimal effects on fat remodeling and adiposity. Surprisingly, double-knockout mice (Cbp/p300-AKO) developed severe lipodystrophy along with marked hepatic steatosis, hyperglycemia and hyperlipidemia. Furthermore, we demonstrated that pharmacological inhibition of Cbp and p300 activity suppressed adipogenesis. Collectively, these data suggest that (i) CBP, but not p300, has distinct functions in regulating fat remodeling and that this occurs in a depot-selective manner; (ii) brown remodeling occurs independently of the improvements in glucose metabolism and obesity and (iii) the combined roles of CBP and p300 are indispensable for normal adipose development.

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Decreased sensitivity to the anorectic effects of leptin in mice that lack a Pomc-specific neural enhancer

PLoS ONE ◽

10.1371/journal.pone.0244793 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244793

Author(s):

Elisa S. Na ◽

Daniel D. Lam ◽

Eva Yokosawa ◽

Jessica M. Adams ◽

David P. Olson ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Knockout Mice ◽

Weight Change ◽

Body Weight Change ◽

Dynamic Regulation ◽

Adult Mice ◽

Environmental Perturbations ◽

Mild Obesity ◽

Over Time

Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been limited. Recently, we have identified two partially redundant enhancers, nPE1 and nPE2, that drive proopiomelanocortin gene expression in the hypothalamus. Here we demonstrate that deletion of nPE1 produces mild obesity while knockout of nPE2 has no discernible metabolic phenotypes. Additionally, we show that acute leptin administration has significant effects on nPE1 knockout mice, with food intake and body weight change significantly impacted by peripheral leptin treatment. nPE1 knockout mice became less responsive to leptin treatment over time as percent body weight change increased over 2 week exposure to peripheral leptin. Both Pomc and Agrp mRNA were not differentially affected by chronic leptin treatment however we did see a decrease in Pomc and Agrp mRNA in both nPE1 and nPE2 knockout calorie restricted mice as compared to calorie restricted PBS-treated WT mice. Collectively, these data suggest dynamic regulation of Pomc by nPE1 such that mice with nPE1 knockout become less responsive to the anorectic effects of leptin treatment over time. Our results also support our earlier findings in which nPE2 may only be critical in adult mice that lack nPE1, indicating that these neural enhancers work synergistically to influence metabolism.

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