miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity

Gaudet, Andrew D.; Fonken, Laura K.; Gushchina, Liubov V.; Aubrecht, Taryn G.; Maurya, Santosh K.; Periasamy, Muthu; Popovich, Phillip G.

doi:10.1038/srep22862

Cited by 90 publications

(95 citation statements)

References 101 publications

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“…172,202,203 In line with these evidences, the current data of the with normal lipoprotein levels did not affect glucose tolerance, presumably due to the low islet miR-155-5p expression level in these mice. 131 Thus, the effect of miR-155-5p…”

Section: Mafb Mediates the Effects Of Mir-155-5p In Isletsmentioning

confidence: 99%

Hyperlipidemia-Induced MicroRNA-155-5p Improves β-Cell Function by TargetingMafb

et al. 2017

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A high-fat diet increases bacterial lipopolysaccharide (LPS) in the circulation and thereby stimulates glucagon-like peptide 1 (GLP-1)–mediated insulin secretion by upregulating interleukin-6 (IL-6). Although microRNA-155-5p (miR-155-5p), which increases IL-6 expression, is upregulated by LPS and hyperlipidemia and patients with familial hypercholesterolemia less frequently develop diabetes, the role of miR-155-5p in the islet stress response to hyperlipidemia is unclear. In this study, we demonstrate that hyperlipidemia-associated endotoxemia upregulates miR-155-5p in murine pancreatic β-cells, which improved glucose metabolism and the adaptation of β-cells to obesity-induced insulin resistance. This effect of miR-155-5p is because of suppression of v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B, which promotes β-cell function through IL-6–induced GLP-1 production in α-cells. Moreover, reduced GLP-1 levels are associated with increased obesity progression, dyslipidemia, and atherosclerosis in hyperlipidemic Mir155 knockout mice. Hence, induction of miR-155-5p expression in β-cells by hyperlipidemia-associated endotoxemia improves the adaptation of β-cells to insulin resistance and represents a protective mechanism in the islet stress response.

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Section: Mafb Mediates the Effects Of Mir-155-5p In Isletsmentioning

confidence: 99%

Hyperlipidemia-Induced MicroRNA-155-5p Improves β-Cell Function by TargetingMafb

et al. 2017

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“…The idea of a potential sexual dimorphism in the expression and/or function of miR‐155 is supported by previous findings (Dai et al, 2013; Longchamps et al, 2014). However, it must be noted that in the same study, the authors report that male miR‐155 KO mice exposed to the HFD did not exhibit a difference in body weight compared to male littermates (Gaudet et al, 2016). While both our study and Gaudet et al used similar obesogenic diets, in our study mice were 10 weeks old when they were exposed to chronic HFD.…”

Section: Discussionmentioning

confidence: 79%

“…We believe that our results highlight important sex differences regarding the contribution of miR‐155 to diet‐induced obesity. A recent study reports that female miR‐155 knockout mice are protected against the obesogenic effects of a HFD (Gaudet et al, 2016). While in our study the increase in body weight of male miR‐155 KO appears to be a consequence of increased intake, female miR‐155 KO, as shown by Gaudet et al, do not exhibit a decrease in intake compared to WT, rather their protection against HFD‐induced body weight appears to be due to an increase in energy expenditure (Gaudet et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study reports that female miR‐155 knockout mice are protected against the obesogenic effects of a HFD (Gaudet et al, 2016). While in our study the increase in body weight of male miR‐155 KO appears to be a consequence of increased intake, female miR‐155 KO, as shown by Gaudet et al, do not exhibit a decrease in intake compared to WT, rather their protection against HFD‐induced body weight appears to be due to an increase in energy expenditure (Gaudet et al, 2016). The idea of a potential sexual dimorphism in the expression and/or function of miR‐155 is supported by previous findings (Dai et al, 2013; Longchamps et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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Down‐regulation of miRNAs in the brain and development of diet‐induced obesity

Maldonado-Avilés

Guarnieri²,

Zhu

et al. 2017

Intl J of Devlp Neuroscience

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Novel therapeutic interventions for obesity and comorbid conditions require knowledge of the molecular elements playing a role in the development of obesity. Chronic low-grade inflammation has been consistently reported in obese individuals. In this study, we first determined whether key molecular modulators of inflammation, microRNA-155 (miR-155) and microRNA-146a (miR-146a), are regulated by an obesogenic diet within brain regions associated with reward, metabolism and energy balance. C57BL/6J mice were chronically exposed to a high-fat diet (HFD) or a standard chow (CTL). Significant reductions in the levels of miR-155 (82%) and miR-146a (41%) levels were observed within the nucleus accumbens of HFD mice compared to CTL. Further analysis of miR-155 regulation showed no significant changes in levels across peripheral tissue (white adipose, spleen, kidney or liver) between HFD and CTL mice. The effect of lower miR-155 on the development of obesity was determined by exposing wild-type (WT) and miR-155 knockout mice (miR-155 KO) to HFD. Male miR-155 KO gained significantly more weight than WT littermates. Metabolic analyses revealed that miR-155 KO significantly ate more HFD compared to WT, without differing in other metabolic measures including energy expenditure. Together, these data show that miR-155 is physiologically down-regulated after intake of an obesogenic diet, and that loss of miR-155 increases intake of an obesogenic diet. Moreover, these findings shed light on a potential miRNA-based mechanism contributing to the development of diet-induced obesity.

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“…Overexpression of miR-155 in endothelial cell inhibits cells proliferation and re-endothelialization and thus increases the permeability of vascular endothelial [10,11]. In addition, miR-155 regulates cardiac fibrosis through TGF-β1-Smad2 signaling pathway, which suggests miR-155 may be a potential therapeutic target for preventing cardiac fibrosis [12,13]. Pharmacological inhibition of miR-155-5p by anti-miRs (antisense oligonucleotides) successfully inhibits cardiac infiltration by monocyte/ macrophages, improves cardiac function and attenuates myocardial damage during viral myocarditis (VM) [14].…”

Section: Introductionmentioning

confidence: 99%