Biology subjects

Munoz, M. D.

Publications and source records attributed to Munoz, M. D..

4 recordsLinked to original sources

bioRxiv2026

Central platelet-rich plasma administration promotes weight loss in diet-induced obese mice

Aims: Platelet-rich plasma (PRP) contains diverse bioactive factors, but its potential role in central regulation of energy balance remains unexplored. This study investigated whether central PRP administration alters metabolic homeostasis in diet-induced obese (DIO) mice and examined associated hypothalamic responses under obese and inflammatory conditions. Materials and Methods: PRP was administered intracerebroventricularly in mouse models of DIO and lipopolysaccharide (LPS)-induced systemic inflammation. Body weight, food intake, energy metabolism, and adiposity were assessed alongside hypothalamic microglial morphology and transcriptomic profiling. Results: A single intracerebroventricular PRP injection reduced body weight in DIO mice, with the effect persisting throughout the 7-day observation period. PRP also decreased cumulative food intake, relative gonadal white adipose tissue weight, and fasting glucose, accompanied by increased energy expenditure, oxygen consumption, fat utilization, and physical activity. In both DIO and LPS-treated mice, PRP reduced IBA1-positive area per microglial cell in the arcuate nucleus without altering microglial number. Hypothalamic RNA sequencing revealed changes in immune and metabolic signaling, extracellular matrix organization, and growth-related pathways, suggesting a complex transcriptional response rather than uniform suppression of inflammation. Conclusions: A single central PRP administration induces sustained weight loss and favorable metabolic changes in DIO mice, accompanied by region-specific hypothalamic microglial and transcriptional responses. These findings identify central PRP as a potential modulator of energy balance and provide a basis for investigating its active components and underlying mechanisms.

neuroscience↗

bioRxiv2025

Protection against diet-induced obesity by a single-point mutation in Kir2.1 channels

High-fat diet (HFD)-induced obesity remains a significant global health challenge. In this study, we show that a global knock-in CRISPR mouse with the Kir2.1L222I single-point mutation exhibits remarkable resistance to HFD-induced obesity. We identify palmitic acid (PA), a prevalent long-chain fatty acid in obesity, as a novel negative regulator of Kir2.1. Kir2.1L222I previously shown to protect against cholesterol-mediated inhibition of Kir2.1, also confers protection against PA-induced suppression. Moreover, PA-induced suppression of Kir2.1 results in a significant loss of flow-induced vasodilation (FIV), while the L222I mutation exerts a protective effect. Notably, Kir2.1L222I mice display significant protection against HFD-induced weight gain and adiposity independent of caloric intake. Specifically, the mutant mice show increased lean mass and decreased fat mass, specifically in both visceral and subcutaneous white adipose tissue (WAT) and intrascapular brown adipose tissue (BAT). Importantly, visceral-to-subcutaneous white adipose ratios decrease while BAT/WAT tissue ratios increase, suggesting a metabolically favorable fat distribution. This protection correlates with enhanced physical activity and increased energy expenditure. Metabolomic analysis reveals elevated TCA cycle metabolites in adipose tissue of Kir2.1L222I mice, consistent with their enhanced energy expenditure. These findings highlight Kir2.1 channels as potential therapeutic targets for obesity and related metabolic disorders.

physiology↗

bioRxiv2025

Medial preoptic area FoxO1 controls metabolic adaptation in a sexually dimorphic manner

The medial preoptic area (MPOA) of the hypothalamus is essential for metabolic adaptation to environmental challenges, though the molecular mechanisms underlying this process remain poorly understood. Here, we investigate the role of Forkhead transcription factor O1 (FoxO1), a key mediator of stress adaptation, in MPOA-dependent metabolic responses to temperature and nutritional changes. Our findings reveal sex-specific responses to both nutritional and temperature challenges. In female mice, but not males, a high-fat diet (HFD) challenge decreased FoxO1 expression in the MPOA. Specific deletion of FoxO1 in MPOA neurons (FoxO1-KOMPOA) had no effect on body weight under normal chow-fed conditions but protected females from HFD-induced obesity (DIO). These protected females exhibited increased lean mass, decreased fat mass, enhanced thermogenesis, increased energy expenditure, and reduced food intake under HFD conditions. They also showed enhanced cold-induced heat production at 6{degrees}C, though this effect vanished at thermoneutrality (30{degrees}C). The protection against DIO was abolished by ovariectomy (OVX) and was not restored by 17{beta}-estradiol supplementation, suggesting an estrogen-independent mechanism. Conversely, constitutive activation of FoxO1 in MPOA neurons (FoxO1-CAMPOA) increased DIO susceptibility in both sexes. Together, these findings demonstrate that FoxO1MPOA plays a crucial role in coordinating metabolic adaptation to nutritional and temperature challenges specifically in female mice.

physiology↗

bioRxiv2021

ORFLine: a bioinformatic pipeline to prioritise small open reading frames identifies candidate secreted small proteins from lymphocytes

The annotation of small open reading frames (smORFs) of less than 100 codons (<300 nucleotides) is challenging due to the large number of such sequences in the genome. The recent development of next generation sequence and ribosome profiling enables identification of actively translated smORFs. In this study, we developed a computational pipeline, which we have named ORFLine, that stringently identifies smORFs and classifies them according to their position within transcripts. We identified a total of 5744 unique smORFs in datasets from mouse B and T lymphocytes and systematically characterized them using ORFLine. We further searched smORFs for the presence of a signal peptide, which predicted known secreted chemokines as well as novel micropeptides. Five novel micropeptides show evidence of secretion and are therefore candidate mediators of immunoregulatory functions.

bioinformatics↗