Dataset Information

Gut microbiota-derived metabolite pantetheine modulates host lipid metabolism to protect against obesity

ABSTRACT:

Obesity is intricately linked to the gut microbiota, yet the microbial effectors and molecular mechanisms that mediate this association remain poorly defined. Fecal microbiome analysis revealed a consistent depletion of the commensal bacterium Roseburia inulinivorans in obese individuals, with its relative abundance inversely correlating with adiposity. This inverse correlation was recapitulated in diet-induced obese mice. Supplementation with R. inulinivorans or its encapsulated form in these mice attenuated high-fat diet-induced weight gain and improved metabolic parameters. Subsequent metabolomic profiling of murine samples identified pantetheine as a key metabolite derived from R. inulinivorans. Administration of pantetheine alone was sufficient to recapitulate the anti-obesity effects observed with bacterial supplementation. Mechanistically, pantetheine modulates adrenergic receptor signaling and directly inhibits lipid droplet accumulation in adipocytes. These findings establish a causal gut-adipose axis wherein R. inulinivorans-derived pantetheine regulates host lipid metabolism to protect against obesity, revealing a novel target for microbiome-based metabolic therapeutics.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13142 | MetaboLights | 2025-10-15

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	a_MTBLS13142_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13142_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13142_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13142_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:The global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed Î²-cell âdysfunctionâ in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies. F0 founders were male Sprague Dawley rats, divided into two groups, high fat (HF) and control. The HF fathers were given commercially prepared high-fat pellets (43% as fat); while the controls ate standard laboratory chow (9% as fat). The two groups of fathers had distinct phenotype; the HF fathers were significantly heavier with increased adiposity, they were also glucose intolerant and insulin resistant. At 15 weeks of age, fathers were mated with normal females consuming chow, to generate the F1 offspring. Only female offspring were studied. Female offspring were weaned unto standard laboratory chow at 3 weeks. At 6 and 12 weeks, intraperitoneal glucose tolerance test (IpGTT) was performed to measure blood glucose and insulin profile; at 11 weeks, intraperitoneal insulin tolerance test was done. The body weight and adiposity of these offspring were not different between the two groups. The HF offspring had glucose intolerance and impaired glucose-induced insulin response, mainly at the acute phase, observed since 6 weeks. The IpITT was not different between groups. At 13 weeks, islets were harvested from the two groups of offspring.

Project description:The global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed M-NM-2-cell M-bM-^@M-^XdysfunctionM-bM-^@M-^Y in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet altered the expression of 211 pancreatic islet genes in adult female offspring (P < 0.001); genes belonged to 8 functional clusters, including calcium ion binding, primary metabolic processes and ATP binding, and organ/system development. Broader KEGG pathway analysis of 2014 genes differentially expressed at the P < 0.01 level further demonstrated involvement of insulin and calcium signaling, and MAPK pathways. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies. F0 founders were male Sprague Dawley rats, divided into two groups: high fat (HF) and control. The HF fathers were given commercially prepared high-fat pellets (43% as fat), while the controls ate standard laboratory chow (9% as fat). The two groups of fathers had distinct phenotypes; the HF fathers were significantly heavier with increased adiposity, and they were also glucose intolerant and insulin resistant. At 15 weeks of age, fathers were mated with normal females consuming chow to generate the F1 offspring. Only female offspring were studied. Female offspring were weaned unto standard laboratory chow at 3 weeks. At 6 and 12 weeks, an intraperitoneal glucose tolerance test (IpGTT) was performed to measure blood glucose and insulin profile; at 11 weeks, an intraperitoneal insulin tolerance test was done. The body weight and adiposity of these offspring were not different between the two groups. The HF offspring had glucose intolerance and impaired glucose-induced insulin response, mainly at the acute phase, observed since 6 weeks. The IpITT was not different between groups. At 14 weeks, fat was harvested from the two groups of offspring.

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Gut microbiota-derived metabolite pantetheine modulates host lipid metabolism to protect against obesity

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