Dietary betaine supplementation increases Fgf21 levels to improve glucose homeostasis and reduce hepatic lipid accumulation in mice

Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans

Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health

Accelerated postnatal growth is a potentially modifiable risk factor for future obesity. To study how specific breast milk components contribute to early growth and obesity risk, we quantified one-carbon metabolism-related metabolites in human breast milk and found an inverse association between milk betaine content and infant growth. This association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in modulating offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content in dams and led to lower adiposity and improved glucose homeostasis throughout adulthood in mouse offspring. These effects were accompanied by a transient increase in Akkermansia spp. abundance in the gut during early life and a long-lasting increase in intestinal goblet cell number. The link between breast milk betaine and Akkermansia abundance in the gut was also observed in humans, as infants exposed to higher milk betaine content during breastfeeding showed higher fecal Akkermansia muciniphila abundance. Furthermore, administration of A. muciniphila to mouse pups during the lactation period partially replicated the effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood. These data demonstrate a link between breast milk betaine content and long-term metabolic health of offspring.info:eu-repo/semantics/acceptedVersio

Immune characterization of long pentraxin 3 in pigs infected with influenza virus

Long pentraxin 3 (PTX3) is a conserved pattern-recognition secreted protein and a host-defence-related component of the humoral innate immune system. The aim of the present study was to characterize swine PTX3 (SwPTX3) protein expression in influenza virus infected pigs. First, we performed in silico studies to evaluate the cross-reactivity of PTX3 human antibodies against SwPTX3. Secondly, we used in vitro analysis to detect SwPTX3 presence in swine bone marrow dendritic cells (SwBMDC) upon stimulation with different agents by Western blot and immunofluorescence. Finally, the levels of SwPTX3 were assessed in experimental infection of pigs with different strains of influenza virus. This is a novel study where the expression of SwPTX3 was evaluated in the context of a pathogen infection. The initial characterization of SwPTX3 in influenza virus infected pigs contributes to understand the role of PTX proteins in the immune response. This work was partly funded by the projects AGL2009-12945-C02-01 and AGL2010-22200-C02-01 by the Spanish Government and FP-7-2008-1, 228394, NADIR project funded by the EU. The contribution of Regione Lombardia (project Metadistretti–SEPSIS), the European Research Council (project HIIS) and the Fondazione Humanitas per la Ricerca is gratefully acknowledged

Dietary betaine supplementation increases Fgf21 levels to improve glucose homeostasis and reduce hepatic lipid accumulation in mice

Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans

Dietary betaine supplementation increases Fgf21 levels to improve glucose homeostasis and reduce hepatic lipid accumulation in mice

Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans