Endogenous Omega-3 Polyunsaturated Fatty Acids Preserved Morphology and Function of Brown Fat Impaired by High-Fat Diet Feeding in Mice

Abstract Objectives The role of omega-3 polyunsaturated fatty acids (PUFA) in regulation of energy homeostasis remains poorly understood. In this study, we aimed to investigate how omega-3 PUFA regulate the morphology and function of brown fat tissue (BAT) in mice. Methods Sixteen-week-old male wild type (WT) and transgenic fat-1 mice, which are capable of synthesizing omega-3 PUFA, were fed a low-fat diet (LFD) or a high-fat diet (HFD) for 13 weeks. Metabolic tissues, including BAT, white adipose tissues, and liver, were collected for biochemical and histological analysis. Results Transgenic fat-1 mice had significantly lower body weight and total fat mass compared with WT mic fed HFD. In addition, fat-1 mice had improved glucose tolerance compared with WT. We found that in WT mice, HFD induced larger lipid droplet accumulation (“whitening”) in BAT, whereas “whitening” in BAT was significantly alleviated in fat-1 mice. Real time PCR showed that some thermogenic markers, such as uncoupling protein 1 (UCP1), carnitine palmitoyltransferase I (CPT I), and cell death activator (CIDE-A), were expressed more in fat-1 mice compared with WT mice fed HFD. Moreover, fat-1 mice had significantly lower lipopolysaccharide levels compared with WT mice. Real time PCR showed that fat-1 mice had significantly lower levels of inflammatory markers, including monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor (TNFα), and mouse macrophage marker (F4/80) in BAT. In a separate experiment, we found that fat-1 mice resisted UCP suppression by LPS injection. Conclusions This study demonstrated that HFD led to obesity and “whitening” of BAT in WT mice; conversely, omega-3 PUFA in fat-1 mice preserved morphology and function of BAT impaired by HFD. We revealed that the dysfunction of BAT may be attributed to increased LPS production due to HFD feeding, and that omega-3 PUFA alleviate the dysfunction of BAT through inhibition of LPS production. Funding Sources This study was supported by the Fortune Education Foundation (New York, USA) and Sansun Life Sciences (Hong Kong, China).

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Omega-3 polyunsaturated fatty acids have beneficial effects on visceral fat in diet-induced obesity model

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0361 ◽

2019 ◽

Vol 97 (6) ◽

pp. 693-701 ◽

Cited By ~ 2

Author(s):

Aline Haas de Mello ◽

Rosiane de Bona Schraiber ◽

Mariana Pereira de Souza Goldim ◽

Khiany Mathias ◽

Carolini Mendes ◽

...

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Energy Intake ◽

Body Mass ◽

Visceral Fat ◽

High Fat Diet ◽

Omega 3 ◽

High Fat ◽

Beneficial Effects ◽

Diet Induced Obesity

This study evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oxidative stress and energy metabolism parameters in the visceral fat of a high-fat-diet induced obesity model. Energy intake, body mass, and visceral fat mass were also evaluated. Male Swiss mice received either a control diet (control group) or a high-fat diet (obese group) for 6 weeks. After this period, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + omega-3, and to these groups 400 mg·(kg body mass)−1·day−1 of fish oil (or saline) was administered orally, for 4 weeks. Energy intake and body mass were monitored throughout the experiment. In the 10th week, the animals were euthanized and the visceral fat (mesenteric) was removed. Treatment with omega-3 PUFAs did not affect energy intake or body mass, but it did reduced visceral fat mass. In visceral fat, omega-3 PUFAs reduced oxidative damage and alleviated changes to the antioxidant defense system and the Krebs cycle. The mitochondrial respiratory chain was neither altered by obesity nor by omega-3 PUFAs. In conclusion, omega-3 PUFAs have beneficial effects on the visceral fat of obese mice because they mitigate changes caused by the consumption of a high-fat diet.

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Aberrant expression of HDL-bound microRNA induced by a high-fat diet in a pig model: implications in the pathogenesis of dyslipidaemia

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02084-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Guoyuan Sui ◽

Lianqun Jia ◽

Nan Song ◽

Dongyu Min ◽

Si Chen ◽

...

Keyword(s):

Real Time ◽

Real Time Pcr ◽

High Fat Diet ◽

Enrichment Analysis ◽

Diet Group ◽

High Fat ◽

Positive Regulation ◽

Aberrant Expression ◽

Balanced Diet ◽

Mirna Sequencing

Abstract Background A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia. Methods Six pigs were randomly divided into two groups of three pigs each, namely, the high-fat diet and the balanced diet groups, which were fed a high-fat diet and balanced diet separately for six months. HDL was separated from plasma, which was followed by dissociation of the miRNA bound to HDL. miRNA sequencing of the isolated miRNA was performed to identify the differential expression profiles between the two groups, which was validated by real-time PCR. TargetScan, miRDB, and miRWalk were used for the prediction of genes targeted by the differential miRNAs. Results Compared with the balanced diet group, the high-fat diet group had significantly higher levels of TG, TC, LDL-C and HDL-C at six months. miRNA sequencing revealed 6 upregulated and 14 downregulated HDL-bound miRNAs in the high-fat diet group compared to the balanced diet group, which was validated by real-time PCR. GO enrichment analysis showed that dysregulated miRNAs in the high-fat diet group were associated with the positive regulation of lipid metabolic processes, positive regulation of lipid biosynthetic processes, and positive regulation of Ras protein signal transduction. Insulin resistance and the Ras signalling pathway were enriched in the KEGG pathway enrichment analysis. Conclusions Twenty HDL-bound miRNAs are significantly dysregulated in high-fat diet-induced dyslipidaemia. This study presents an analysis of a new set of HDL-bound miRNAs that are altered by a high-fat diet and offers some valuable clues for novel mechanistic insights into high-fat diet-induced dyslipidaemia. Further functional verification study using a larger sample size will be required.

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DHA-enriched phospholipids from large yellow croaker roe regulate lipid metabolic disorders and gut microbiota imbalance on SD rats with a high-fat diet

Food & Function ◽

10.1039/d1fo00747e ◽

2021 ◽

Author(s):

Xiaodan Lu ◽

Rongbin Zhong ◽

Ling Hu ◽

Luyao Huang ◽

Lijiao Chen ◽

...

Keyword(s):

Fatty Acids ◽

Docosahexaenoic Acid ◽

Gut Microbiota ◽

Polyunsaturated Fatty Acids ◽

High Fat Diet ◽

Nutritional Value ◽

Metabolic Disorders ◽

Large Yellow Croaker ◽

High Fat ◽

Sd Rats

Abstract Large yellow croaker roe phospholipids (LYCRPLs) has great nutritional value because of containing rich docosahexaenoic acid (DHA), which is a kind of n-3 polyunsaturated fatty acids (n-3 PUFAs). In...

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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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High ratio of ω-3/ω-6 polyunsaturated fatty acids targets mTORC1 to prevent high-fat diet-induced metabolic syndrome and mitochondrial dysfunction in mice

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2019.108330 ◽

2020 ◽

Vol 79 ◽

pp. 108330 ◽

Cited By ~ 4

Author(s):

Run Liu ◽

Lei Chen ◽

Yan Wang ◽

Guanfei Zhang ◽

Ying Cheng ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

High Ratio ◽

High Fat

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High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats

Clinical Epigenetics ◽

10.1186/s13148-020-00974-7 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Sharvari S. Deshpande ◽

Harishankar Nemani ◽

Gandhimathi Arumugam ◽

Avinash Ravichandran ◽

Nafisa H. Balasinor

Keyword(s):

Dna Methylation ◽

Real Time ◽

Real Time Pcr ◽

High Fat Diet ◽

Male Rats ◽

Global Dna Methylation ◽

High Fat ◽

Differential Effects ◽

Male Germline ◽

Embryo Loss

Abstract Background Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes. Earlier we had demonstrated differential effects of high-fat diet-induced obesity (DIO) and genetically inherited obesity (GIO) on metabolic, hormonal profile, male fertility, and spermatogenesis using two rat models. The present study aimed to understand the effect of DIO and GIO on DNA methylation in male germline, and its subsequent effects on the resorbed (post-implantation embryo loss) and normal embryos. First, we assessed the DNA methylation enzymatic machinery in the testis by Real-Time PCR, followed global DNA methylation levels in spermatozoa and testicular cells by ELISA and flow cytometry, respectively. Further, we performed Methylation Sequencing in spermatozoa for both the groups. Sequencing data in spermatozoa from both the groups were validated using Pyrosequencing. Expression of the differentially methylated genes was assessed in the resorbed and normal embryos sired by the DIO group using Real-Time PCR for functional validation. Results We noted a significant decrease in Dnmt transcript and global DNA methylation levels in the DIO group and an increase in the GIO group. Sequencing analysis showed 16,966 and 9113 differentially methylated regions in the spermatozoa of the DIO and GIO groups, respectively. Upon pathway analysis, we observed genes enriched in pathways involved in embryo growth and development namely Wnt, Hedgehog, TGF-beta, and Notch in spermatozoa for both the groups, the methylation status of which partially correlated with the gene expression pattern in resorbed and normal embryos sired by the DIO group. Conclusion Our study reports the mechanism by which diet-induced and genetically inherited obesity causes differential effects on the DNA methylation in the male germline that could be due to a difference in the white adipose tissue accumulation. These differences could either lead to embryo loss or transmit obesity-related traits to the offspring in adult life.

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Postnatal Dietary Omega-3 Fatty Acid Supplementation Rescues Glucocorticoid-Programmed Adiposity, Hypertension, and Hyperlipidemia in Male Rat Offspring Raised on a High-Fat Diet

Endocrinology ◽

10.1210/en.2013-1153 ◽

2013 ◽

Vol 154 (9) ◽

pp. 3110-3117 ◽

Cited By ~ 15

Author(s):

Intan S. Zulkafli ◽

Brendan J. Waddell ◽

Peter J. Mark

Keyword(s):

Blood Pressure ◽

Fatty Acids ◽

High Fat Diet ◽

Plasma Cholesterol ◽

Adverse Outcomes ◽

Male Rat ◽

Delayed Puberty ◽

Adult Offspring ◽

Omega 3 ◽

High Fat

Fetal glucocorticoid excess programs several adverse outcomes in adult offspring, many of which can be prevented by postnatal, dietary omega-3 (n-3) fatty acids. Here we tested 2 separate hypotheses: 1) a postnatal high-fat diet exacerbates the glucocorticoid-programmed phenotype; and 2) postnatal, dietary n-3 fatty acids rescue programmed outcomes, even in the presence of a high-fat diet challenge. Pregnant Wistar rat dams were either untreated or administered dexamethasone acetate (Dex; 0.5 μg/mL drinking water) from day 13 of pregnancy. Offspring were cross-fostered to untreated mothers and males were weaned onto a standard (Std), high-fat, low n-3 (HF), or high-fat, high n-3 (HFHn-3) diet. Prenatal Dex reduced birth weight (26%) and delayed puberty onset by 1.2 days, irrespective of postnatal diet. Prenatal Dex programmed increased blood pressure in adult offspring, an effect worsened by the postnatal HF diet. Supplementation with high n-3 fatty acids, however, prevented both the Dex and HF-induced increases in blood pressure. Prenatal Dex also programmed increased adiposity, plasma cholesterol, and plasma triglyceride levels at 6 months of age, particularly in those offspring raised on the HF diet. But again, each of these adverse outcomes was rescued by supplementation of the HF diet with n-3 fatty acids. In conclusion, the capacity of n-3 fatty acids to overcome adverse programming outcomes remains evident, even in the presence of a HF diet challenge.

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