Biology subjects

Lee, M.-L.

Publications and source records attributed to Lee, M.-L..

3 recordsLinked to original sources

bioRxiv2024

Hypothalamic prostaglandins facilitate recovery from hypoglycemia but exacerbate recurrent hypoglycemia in mice

The hypothalamus monitors blood glucose levels and regulates glucose production in the liver. In response to hypoglycemia, glucose-inhibited (GI) neurons trigger counter-regulatory responses (CRRs), which stimulate the release of glucagon, epinephrine, and cortisol to elevate blood glucose. Recurrent hypoglycemia (RH), however, reduces the effectiveness of these CRRs. This study examined the role of hypothalamic prostaglandins in glucose recovery during acute hypoglycemia and RH. Using imaging mass spectrometry and liquid chromatography/mass spectrometry, phospholipid and prostaglandin levels in the hypothalamus of C57BL mice were increased following insulin or 2-deoxy-glucose administration. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), was infused into the ventromedial hypothalamus (VMH) to analyze its effect on glucose production during hypoglycemia, revealing that prostaglandin inhibition decreased glucagon secretion. Additionally, RH-treated mice decreased glucagon release and glucose production during hypoglycemia. Inhibiting prostaglandin production via short-hairpin RNA against cytosolic phospholipase A2 (cPLA2) in the hypothalamus restored CRRs diminished by RH via increasing glucagon sensitivity. These findings suggest that hypothalamic prostaglandins play a critical role in glucose recovery from acute hypoglycemia by activating VMH neurons and are also crucial for the attenuation of CRRs during RH. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/600540v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@9e2cf0org.highwire.dtl.DTLVardef@984c29org.highwire.dtl.DTLVardef@b04e6borg.highwire.dtl.DTLVardef@ec6dd3_HPS_FORMAT_FIGEXP M_FIG C_FIG Article HighlightsO_LIInsulin decreases arachidonic acid-containing phospholipids and increases prostaglandin production in the hypothalamus. C_LIO_LIProstaglandin in the hypothalamus increases glucagon secretion and glucose production during hypoglycemia. C_LIO_LIRecurrent hypoglycemia decreases glucagon secretion and glucose production during hypoglycemia. C_LIO_LIProstaglandin in the hypothalamus during recurrent hypoglycemia decreases glucagon sensitivity and glucose production. C_LI

neuroscience↗

bioRxiv2020

Activation of prodynorphin neurons in the dorsomedial hypothalamus inhibits food intake and promotes positive valence

The regulation of food intake is one of the major research areas in the study of metabolic syndromes such as obesity. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behaviour. However, our understanding of neural function under physiological conditions is still limited. Immediate early genes, such as activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), are useful markers of neuronal activity. Here, we investigated the role of Arc/Arg3.1 gene-expressing neurons in the hypothalamus after refeeding using the targeted recombination in active populations method. We identified refeeding-responsive prodynorphin/cholecystokinin neurons in the dorsomedial hypothalamus that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of these neurons decreased food intake and promoted positive valence. Our findings provide insight into the role of newly identified hedonic neurons in the process of feeding-induced satiety.

physiology↗

bioRxiv2020

Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism

The hypothalamus plays a central role in monitoring and regulating systemic glucose metabolism. The brain is enriched with phospholipids containing poly-unsaturated fatty acids, which are biologically active in physiological regulation. Here, we show that intraperitoneal glucose injection induced changes in hypothalamic distribution and amount of phospholipids, especially arachidonic-acid-containing phospholipids, that were then metabolized to produce prostaglandins. Knockdown of cytosolic phospholipase A2 (cPLA2), a key enzyme for generating arachidonic acid from phospholipids, in the hypothalamic ventromedial nucleus (VMH), lowered insulin sensitivity in muscles during regular chow diet (RCD) feeding. Conversely, the down-regulation of glucose metabolism by high fat diet (HFD) feeding was improved by knockdown of cPLA2 in the VMH through changing hepatic insulin sensitivity and hypothalamic inflammation. Our data suggest that cPLA2-mediated hypothalamic phospholipid metabolism is critical for controlling systemic glucose metabolism during RCD, while continuous activation of the same pathway to produce prostaglandins during HFD deteriorates glucose metabolism.

physiology↗