Biology subjects

Leiria, L. O.

Publications and source records attributed to Leiria, L. O..

3 recordsLinked to original sources

bioRxiv2026

Cold acclimation reprograms hepatic lipid composition toward n-3 HUFAs to uncouple adipose-derived lipid flux from steatosis

While cold exposure drives lipid flux from adipose tissue to the liver, this enhanced inter-organ crosstalk does not result in sustained hepatic steatosis during prolonged acclimation, indicating that factors beyond lipid flux shape metabolic outcome. To interrogate this adaptation, we performed integrated lipidomic and metabolic profiling across tissues and circulating lipoproteins over the course of cold acclimation. We showed that cold acclimation induces systemic reprogramming of lipid quality in mice, characterized by enrichment of n-3 highly unsaturated fatty acids (HUFAs) as a consequence of upregulation of fatty acid desaturases (FADS1 and 2) in the liver and white adipose tissue, thus increasing hepatic n-3/n-6 ratio. Cold-induced increase in n-3 HUFAs cause the suppression of SCD1-mediated desaturation, thus yielding a depletion of monounsaturated fatty acids (MUFAs) in the liver, along with the suppression of lipogenic markers. Notably, this high-HUFA/low-MUFA lipid signature is present in both hepatic free fatty acid and triglyceride pools, indicating that lipid remodeling occurs upstream of triglyceride synthesis. Lipidomic analysis revealed that the remodeled triglycerides are incorporated into very-low-density and intermediate density lipoproteins (VLDL and IDL), thereby propagating hepatic lipid reprogramming to the circulation. Thus, by selectively increasing endogenous n-3 HUFA availability, cold adaptation suppresses hepatic DNL and MUFA-driven triglyceride assembly, buffering lipid accumulation despite sustained fatty acid influx and reshaping systemic lipid distribution with potential cardiometabolic impact.

biochemistry↗

bioRxiv2025

E4BP4 Safeguards Brown Fat Mitochondria from Obesity-Induced Fragmentation via Ceramide Repression

Brown adipose tissue (BAT) counteracts obesity-related metabolic dysfunction through both thermogenic and non-thermogenic means. However, substantial evidence indicates that obesity negatively affects BAT mitochondrial morphology and oxidative capacity, impairing systemic energy homeostasis. Motivated by this apparent contradiction, we investigated the relationship between obesity and mitochondrial dynamics, as the underlying mechanisms remain incompletely understood. Here, we identified E4BP4 as a transcriptional repressor that prevents obesity-induced mitochondrial fragmentation and oxidative dysfunction by inhibiting ceramide synthesis in brown fat. Specifically, E4BP4 interacts with PRDM16 to repress Cers6 mRNA expression and consequently reduces C16:0 ceramide levels by binding to a 65 kb upstream enhancer region of the Cers6 gene. Notably, the preservation of mitochondrial integrity in BAT by E4BP4 gain-of-function improves systemic glucose homeostasis, independent of weight loss. Collectively, our findings establish E4BP4 as a molecular safeguard against obesity-induced mitochondrial fragmentation and oxidative dysfunction, primarily by suppressing ceramide synthesis in brown fat.

physiology↗

bioRxiv2025

Non-invasive and unbiased assessment of thermogenesis in mice through thermal gradient ring

Accurately assessing whole-body heat production requires reliable thermometry methods. In mice, common approaches include rectal temperature (RT) measurement, infrared (IR) thermography, and implanted probes. However, factors such as stress, handling, surgery, and variability limit their applicability for evaluating thermogenesis. The Thermal Gradient Ring (TGR), widely used in neuropathic pain and ion channel studies, consists of a circular structure with twelve temperature zones and an integrated IR camera for real-time behavior monitoring. This system allows precise analysis of preferred temperature (PT), heat tolerance, locomotion, and zone occupancy over time, thereby offering a behavioral perspective beyond traditional thermometric methods, which provides only temperature data. In this study, we evaluated TGR as a non-invasive tool for detecting thermogenic changes. Since mice with higher thermogenesis prefer cooler zones, while those with reduced thermogenesis seek warmth, TGR provides a sensitive readout of metabolic behavior. Using models with both enhanced and impaired thermogenesis, we demonstrated TGRs ability to detect thermogenic status under different conditions. These findings suggest that TGR is a valuable tool for metabolic research, offering a reliable alternative for assessing thermogenesis in mice.

physiology↗