Selective inhibition of intestinal 5-HT improves neurobehavioral abnormalities caused by high-fat diet mice

Pan, Qi; Liu, Qiongzhen; Wan, Renling; Kalavagunta, Praveen Kumar; Liu, Li; Lv, Wenting; Qiao, Tong; Shang, Jing; Wu, Huali

doi:10.1007/s11011-019-0392-x

Cited by 23 publications

(13 citation statements)

References 82 publications

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“…Pan et al treated male C57BL/6 DIO mice with a selective, intestinal serotonin blocker, decreasing serotonin serum and intestine levels. They found a slowing in weight gain and improved blood glucose and lipid values compared to controls [104]. Besides endogenous serotonin, treating rats fed a standard diet with antibiotics lowered plasmatic indole-3-propionic acid, a tryptophan gut bacteria derivative, and displayed higher weight gain in animals [105].…”

Section: Tryptophan As Another Potential Treatment For Obesitymentioning

confidence: 97%

Protein, amino acids and obesity treatment

Simonson

Boirie‌

Guillet

2020

Rev Endocr Metab Disord

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Dietary proteins have been used for years to treat obesity. Body weight loss is beneficial when it concerns fat mass, but loss of fat free massespecially muscle might be detrimental. This occurs because protein breakdown predominates over synthesis, thus administering anabolic dietary compounds like proteins might counter fat free mass loss while allowing for fat mass loss. Indeed, varying the quantity of proteins will decrease muscle anabolic response and increase hyperphagia in rodents fed a low protein diet; but it will favor lean mass maintenance and promote satiety, in certain age groups of humans fed a high protein diet. Beyond protein quantity, protein source is an important metabolic regulator: whey protein and plant based diets exercize favorable effects on the risk of developing obesity, body composition, metabolic parameters or fat free mass preservation of obese patients. Specific amino-acids like branched chain amino acids (BCAA), methionine, tryptophan and its metabolites, and glutamate can also positively influence parameters and complications of obesity especially in rodent models, with less studies translating this in humans. Tuning the quality and quantity of proteins or even specific amino-acids can thus be seen as a potential therapeutic intervention on the body composition, metabolic syndrome parameters and appetite regulation of obese patients. Since these effects vary across age groups and much of the data comes from murine models, long-term prospective studies modulating proteins and amino acids in the human diet are needed.

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Section: Tryptophan As Another Potential Treatment For Obesitymentioning

confidence: 97%

Protein, amino acids and obesity treatment

Simonson

Boirie‌

Guillet

2020

Rev Endocr Metab Disord

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“…4g). Previous studies have also reported the potential of their neuroprotective effects 13,14,36 . Administration of all these metabolites individually improved cognitive function and insulin sensitivity in db/db mice ( Fig.…”

Section: Fdrmentioning

confidence: 99%

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

et al. 2020

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Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, restructures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.

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“…High fat fed mice have increased levels of 5‐HT in serum and in BAT, and inhibition of peripheral 5‐HT synthesis reduces their adiposity, metabolic dysfunction, and hepatic steatosis . This effect was at least partially attributed to increased β3‐adrenergic induction of UCP1‐mediated, BAT thermogenesis .…”

Section: Discussionmentioning

confidence: 99%

Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT_1A receptor activation in raphe pallidus

et al. 2019

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Aim Serotonin (5‐hydroxytryptamine, 5‐HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5‐HT. Methods Electrophysiological recordings, intravenous (iv) injections and nanoinjections in the brains of anaesthetized rats. Results Cooling‐evoked increases in BAT SNA were inhibited by the intra‐rostral raphé pallidus (rRPa) and the iv administration of the 5‐HT1A receptor agonist, 8‐OH‐DPAT or 5‐HT. The intra‐rRPa 5‐HT, the intra‐rRPa and the iv 8‐OH‐DPAT, but not the iv 5‐HT‐induced inhibition of BAT SNA were prevented by nanoinjection of a 5‐HT1A receptor antagonist in the rRPa. The increase in BAT SNA evoked by nanoinjection of NMDA in the rRPa was not inhibited by iv 5‐HT, indicating that iv 5‐HT does not inhibit BAT SNA by acting in the rRPa or in the sympathetic pathway distal to the rRPa. In contrast, under a warm condition, blockade of 5HT1A receptors in the rRPa increased BAT SNA and BAT thermogenesis, suggesting that endogenous 5‐HT in the rRPa contributes to the suppression of BAT SNA and BAT thermogenesis. The increases in BAT SNA and BAT thermogenesis evoked by nanoinjection of NMDA in the dorsomedial hypothalamus (DMH) were inhibited by iv 5‐HT, but those following bicuculline nanoinjection in the DMH were not inhibited. Conclusions The systemic 5‐HT‐induced inhibition of BAT SNA requires a GABAergic inhibition of BAT sympathoexcitatory neurones in the DMH. In addition, during warming, 5‐HT released endogenously in rRPa inhibits BAT SNA.

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Selective inhibition of intestinal 5-HT improves neurobehavioral abnormalities caused by high-fat diet mice

Cited by 23 publications

References 82 publications

Protein, amino acids and obesity treatment

Protein, amino acids and obesity treatment

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT_1A receptor activation in raphe pallidus

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Selective inhibition of intestinal 5-HT improves neurobehavioral abnormalities caused by high-fat diet mice

Cited by 23 publications

References 82 publications

Protein, amino acids and obesity treatment

Protein, amino acids and obesity treatment

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus

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Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT_1A receptor activation in raphe pallidus