Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice

Yang, Jinchunzi; Sáinz, Neira; Félix‐Soriano, Elisa; Gil‐Iturbe, Eva; Castilla‐Madrigal, Rosa; Fernández‐Galilea, Marta; Martínéz, J. Alfredo; Moreno-Aliaga, María J.

doi:10.3390/nu13020501

Cited by 19 publications

(13 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The metabolic changes that occurred during aging were aggravated in the aged DIO mice, which accumulated more fat and exhibited a worsened hyperglycemia, hyperinsulinemia, and dyslipidemia (Table 1). Chronic feeding with the DHA‐rich diet (aged DIOMEG group) tended to reduce body weight 38,47 and fat accumulation especially in the white adipose depots, in parallel with improved total chol, LDL‐chol, and the atherogenic index LDL‐chol/HDL‐chol compared to the aged DIO group, without significantly affecting fasting glucose and insulin levels (Table 1). Thus, long‐term feeding with a DHA‐enriched HFD improved lipid serum profile as compared to aged DIO animals but had no significant effects on body composition and glucose metabolism biomarkers as compared to aged DIO mice.…”

Section: Resultsmentioning

confidence: 99%

“…The different HFDs (prepared by Research Diets Inc) were vacuum sealed in 2.5 kg plastic bags and kept frozen (−20°C) until used to avoid rancidity. Specific dietary compositions can be found in a recent manuscript of our group 38 …”

Section: Methodsmentioning

confidence: 99%

“…Specific dietary compositions can be found in a recent manuscript of our group. 38 F I G U R E 1 Animal experimental design. After 10 days of acclimation, 2-month-old (young CT) mice were sacrificed.…”

Section: Animal Study Designmentioning

confidence: 99%

See 2 more Smart Citations

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to chronic unresolved inflammation, which could be mediated by an impaired production of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs, Resolvins-Rvs, Protectins-PDs, and Maresins-MaRs. Our aim was to characterize the changes in BAT SPMs signatures and their association with BAT dysfunction during aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic acid (DHA)-rich diet. Lipidomic, functional, and molecular studies were performed in BAT of 2-and 18-month-old lean (CT) female mice and in 18-month-old diet-induced obese (DIO) mice fed with a high-fat diet (HFD), or a DHA-enriched HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice, while DHA partially restored them. Arachidonic acid (AA)-derived LXs and DHAderived MaRs and PDs were the most abundant SPMs in BAT of young CT mice.Research (University of Navarra). JD is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant 107613/Z/15/Z) Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice compared to young CT mice. Some of the SPMs most significantly reduced in obeseaged mice included LXB 4 , MaR2, 4S,14S-diHDHA, 10S,17S-diHDHA (a.k.a. PDX), and RvD6. In contrast, DHA increased DHA-derived SPMs, without modifying LXs.However, MicroPET studies showed that DHA was not able to counteract the impaired cold exposure response in BAT of obese-aged mice. Our data suggest that a defective SPMs production could underlie the decrease of BAT activity observed in obese-aged mice, and highlight the relevance to further characterize the physiological role and therapeutic potential of specific SPMs on BAT development and function.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, exercise was shown to downregulate TLR4 expression in muscle and leukocytes in humans [ 39 , 40 ], and in muscle, vascular tissue, blood cells, and adipose tissue in mice [ 41 ]. Yang et al also showed that exercise ameliorated TLR4 mRNA levels in NAFLD mice [ 42 ]. Similarly, our results showed that the mRNA levels of MD2 and TLR4 were both decreased by exercise.…”

Section: Discussionmentioning

confidence: 99%

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Zhu

Sahar

Javaid

et al. 2021

Cells

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.

show abstract

“…Table 1 shows a list of used primers that were previously described in other studies and verified with Primer-Blast software (National Center for Biotechnology Information, Bethesda, MD, USA). As previously described, 36b4 was used as a housekeeping gene [29][30][31].…”

Section: Rna Extraction and Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease, Hepatic Fibrosis, and Insulin Resistance in Mice

et al. 2021

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient; MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.

show abstract

Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice

Cited by 19 publications

References 133 publications

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease, Hepatic Fibrosis, and Insulin Resistance in Mice

Contact Info

Product

Resources

About