Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.

There are a number of distinct signatures of superfluids, one of which is the appearance of quantized vortices. There have been some attempts to understand the putative supersolid 4He in the vortex framework, but no conclusive evidence that supports the existence of the vortices has been reported. Here, we investigate the rotation velocity dependence of the torsional oscillation of solid 4He at various temperatures. The velocity sweep reveals intriguing periodic staircaselike features below about 300 mK. The staircase patterns show remarkable periodicity, and we interpret these patterns as a consequence of vortex injection. However, there are some features that cannot be accounted for with simple injection of vortices into superfluid, and further investigation is required.

Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of β cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased β cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in β cells. Secreted serotonin stimulated β cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved β cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing β cell proliferation and reducing oxidative stress in β cells.

Serotonin is a biogenic amine synthesized from the essential amino acid tryptophan. Because serotonin cannot cross the blood-brain barrier, it functions differently in neuronal and non-neuronal tissues. In the CNS, serotonin regulates mood, behavior, appetite, and energy expenditure. Although most serotonin in the body is synthesized at the periphery, its biological roles have not been well elucidated. Older studies using chemical agonists and antagonists yielded conflicting results, because the complexity of serotonin receptors and the low selectivity of agonists and antagonists were not known. Several recent studies using specific knock-out of serotonin receptors have been performed to assess the role of peripheral serotonin in regulating energy metabolism. This review discusses (1) the tissue-specific roles of peripheral serotonin in regulating energy metabolism, (2) the mechanism by which dysfunctional peripheral serotonin signaling can progress to metabolic diseases, and (3) how peripheral serotonin signaling could be a therapeutic target for metabolic diseases.

We apply a low-frequency ͑mHz͒ ac pressure gradient to a sample of solid helium in order to search for a superfluidlike response. Our results are consistent with zero supersolid flow. Through a statistical analysis of our data, we set a bound on the rate of mass flow between two chambers, and hence the mass current density j. At the 68% confidence level, we bound v ϵ j / Յ 9.6ϫ 10 −4 nm/ s for the mass transport velocity. In terms of a simple model for the supersolid, we find an upper bound of 8.4ϫ 10 −6 for the supersolid fraction at 25 mK, at this same confidence level. These findings force the conclusion that the NCRI observed in the torsional oscillator experiments is not evidence for a frequency-independent superfluidlike state. Supersolid behavior is a frequency-dependent phenomenon, clearly evident at frequencies above 100 Hz of the torsional oscillator experiments, but undetectably small at frequencies approaching zero.