High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome

Hassan, Ahmed M.; Mancano, Giulia; Kashofer, Karl; Fröhlich, Esther E.; Matak, Andrija; Mayerhofer, Raphaela; Reichmann, Florian; Olivares, Marta; Neyrinck, Audrey M.; Claus, Sandrine P.; Holzer, Peter

doi:10.1080/1028415x.2018.1465713

Cited by 136 publications

(102 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the TST and the forced swim stress have been developed to screen antidepressant-like activity rather than to ascertain depressive-like behavior (Nestler and Hyman, 2010). The observation that HFD leads to anhedonia and decreased self-care (Dutheil et al, 2016;Zemdegs et al, 2016) reinforces the idea that core symptoms of depression can be also affected by HFD-induced IR (Miyata et al, 2004;Abildgaard et al, 2011;Ho et al, 2012;André et al, 2014;Gupta et al, 2014;Liu et al, 2014;Dutheil et al, 2016;Yang et al, 2016;Zemdegs et al, 2016;Hassan et al, 2018). These data mirror the clinical observations that people experiencing type 2 diabetes and IR are twice as likely to develop depression compared to people without diabetes de Groot et al, 2001).…”

Section: Discussionmentioning

confidence: 72%

“…Evidence also suggests the existence of a positive correlation between IR and major depression (Rasgon and Kenna, 2005). Indeed, the induction of IR in rats or mice, using prolonged exposure to high-fat diet (HFD), causes some hallmark symptoms of depression including anxiety, anhedonia, and despair (Miyata et al, 2004;Ho et al, 2012;André et al, 2014;Gupta et al, 2014;Dutheil et al, 2016;Yang et al, 2016;Zemdegs et al, 2016;Hassan et al, 2018) and exacerbates behavioral abnormalities observed in animal models of depression (Abildgaard et al, 2011;Liu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

et al. 2019

View full text Add to dashboard Cite

Epidemiological studies indicate that insulin resistance (IR), a hallmark of type 2 diabetes, is associated with an increased risk of major depression. Here, we demonstrated that male mice fed a high-fat diet (HFD) exhibited peripheral metabolic impairments reminiscent of IR accompanied by elevated circulating levels of branched-chain amino acids (BCAAs), whereas both parameters were normalized by chronic treatment with metformin (Met). Given the role of BCAAs in the regulation of tryptophan influx into the brain, we then explored the activity of the serotonin (5-HT) system. Our results indicated that HFD-fed mice displayed impairment in the electrical activity of dorsal raphe 5-HT neurons, attenuated hippocampal extracellular 5-HT concentrations and anxiety, one of the most visible and early symptoms of depression. On the contrary, Met stimulated 5-HT neurons excitability and 5-HT neurotransmission while hindering HFD-induced anxiety. Met also promoted antidepressant-like activities as observed with fluoxetine. In light of these data, we designed a modified HFD in which BCAA dietary supply was reduced by half. Deficiency in BCAAs failed to reverse HFD-induced metabolic impairments while producing antidepressant-like activity and enhancing the behavioral response to fluoxetine. Our results suggest that Met may act by decreasing circulating BCAAs levels to favor serotonergic neurotransmission in the hippocampus and promote antidepressant-like effects in mice fed an HFD. These findings also lead us to envision that a diet poor in BCAAs, provided either alone or as add-on therapy to conventional antidepressant drugs, could help to relieve depressive symptoms in patients with metabolic comorbidities.Insulin resistance in humans is associated with increased risk of anxiodepressive disorders. Such a relationship has been also found in rodents fed a high-fat diet (HFD). To determine whether insulin-sensitizing strategies induce anxiolytic-and/or antidepressant-like activities and to investigate the underlying mechanisms, we tested the effects of metformin, an oral antidiabetic drug, in mice fed an HFD. Metformin reduced levels of circulating branched-chain amino acids, which regulate tryptophan uptake within the brain. Moreover, metformin increased hippocampal serotonergic neurotransmission while promoting anxiolytic-and antidepressant-like effects. Moreover, a diet poor in these amino acids produced similar beneficial behavioral property. Collectively, these results suggest that metformin could be used as add-on therapy to a conventional antidepressant for the comorbidity between metabolic and mental disorders.

show abstract

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Based on previous work [3] we hypothesized that the effect of HFD to alter the brain metabolome and cause anhedonia-like behavior is due to a change in the intestinal microbiota. The current findings provided conclusive evidence for such a relationship, since the HFDinduced decrease in sucrose preference and self-care was absent in antibiotic-treated mice.…”

Section: Antibiotic-induced Microbiota Depletion Prevented Hfd-inducementioning

confidence: 99%

“…Epidemiological studies have revealed that obesity and imbalanced nutrition increase the risk for depressive disorders [1,2]. Likewise, long-term exposure of rodents to an obesogenic diet leads to a depression-like phenotype which includes anhedonia [3][4][5][6][7]. Anhedonia is a core symptom of depression [8,9], and comprehension of the mechanisms underlying anhedonia in animal models of obesity may explain the interrelationship between obesity and depression.…”

Section: Introductionmentioning

confidence: 99%

“…HFD induces anhedonia-like behavior in mice which is associated with distinct alterations in the intestinal microbiota and brain metabolome [3]. The major aims of the current work were (i) to obtain conclusive evidence that the gut microbiota plays an indispensable role in HFD-induced anhedonia-like behavior and (ii) to identify a hormonal mechanism that links diet and intestinal microbiota to anhedonia-like behavior.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anhedonia induced by high-fat diet in mice depends on gut microbiota and leptin

Hassan

Mancano

Kashofer

et al. 2020

Nutritional Neuroscience

Self Cite

View full text Add to dashboard Cite

Objectives: Imbalanced nutrition and obesity are risk factors for depression, a relationship that in rodents can be modeled by depression-like behavior in response to high-fat diet (HFD). In this work, we examined the role of the intestinal microbiota and the adipocytokine leptin as potential mediators of the effects of HFD to induce anhedonia-like behavior and reduce self-care in mice. Methods: Male mice were fed a control diet or HFD (60 kJ% from fat) for a period of 4 weeks, after which behavioral tests and molecular analyses (gut microbiome composition, intestinal metabolome, fecal fatty acids, plasma hormone levels) were performed. The role of the intestinal microbiota was addressed by selective depletion of gut bacteria with a combination of non-absorbable antibiotics, while the implication of leptin was examined by the use of leptin-deficient ob/ob mice. Results: Antibiotic treatment reduced the HFD-induced weight gain and adiposity and prevented HFD-induced anhedonia-like behavior and self-care reduction. These effects were associated with a decrease in fecal fatty acids and intestinal microbiota-related metabolites including short-chain fatty acids, glucose and amino acids. Gut microbiota depletion suppressed the HFD-induced rise of plasma leptin, and the circulating leptin levels correlated with the anhedonia-like behavior and reduced selfcare caused by HFD. The anhedonic effect of HFD was absent in leptin-deficient ob/ob mice although these animals gained more weight and adiposity in response to HFD than wild-type mice. Discussion: The results indicate that anhedonia-like behavior induced by HFD in mice depends on the intestinal microbiome and involves leptin as a signaling hormone.

show abstract

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

View full text Add to dashboard Cite

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

show abstract

High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome

Cited by 136 publications

References 62 publications

Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

Anhedonia induced by high-fat diet in mice depends on gut microbiota and leptin

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Contact Info

Product

Resources

About