Biology subjects

Kipp, Z. A.

Publications and source records attributed to Kipp, Z. A..

3 recordsLinked to original sources

bioRxiv2026

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling

Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature. Yet how these diverse signals are molecularly integrated remains unknown. Here we show that clock, diet, and temperature cues converge on the orphan mitochondrial transporter, SLC25A34, to orchestrate thermogenic cycling of lipid synthesis and oxidation. During sleep, the clock suppresses Slc25a34 transcription through REV-ERB. Waking, lipid-rich diets, or cold exposure abolish this repression, allowing lipolytic signals to stimulate Slc25a34 expression via PPAR. SLC25A34 then imports oxaloacetate into mitochondria to accelerate the export of substrates used for acetyl-CoA production in the cytosol. This feeds into cytosolic lipid synthesis and transcriptional induction of mitochondrial biogenesis, which collectively promote mitochondrial lipid oxidation. Thus, SLC25A34 confers circadian, dietary, and environmental control of thermogenic metabolism through interorganellar lipid cycling.

molecular biology↗

bioRxiv2025

A comparison of adiponectin-deficient mice reveals the fundamental role of intracellular adiponectin

Adiponectin is an important adipokine with insulin-sensitizing, anti-inflammatory, and anti-fibrotic properties. The physiological roles of adiponectin have been studied using global adiponectin knockout (KO) mice. However, the reported phenotypes of adiponectin KO mice vary based on the mouse lines generated by different strategies and investigators. We performed a head-to-head comparison of the adiponectin KO mice that were generated in Dallas, Houston and Osaka. RNAseq revealed that the expression of the bioactive domain of adiponectin - the globular domain - was preserved in the Houston and Osaka KO mice. A complete adiponectin KO model, such as the Dallas KO mouse, exhibits a lower body weight, the highest adipocyte mitochondrial function and displays a susceptibility to DNA damage-mediated lung fibrosis. The reconstitution of globular adiponectin into the Dallas KO mice prompted an increase in body weight and a partial recapitulation of the Osaka KO model transcriptome signature. The intracellular globular adiponectin form is important, as we found that globular adiponectin enhances PPAR{gamma} activity by modulating the coregulators interacting with PPAR{gamma}. Overall, the residual expression of globular adiponectin regulates adipose tissue metabolism by altering PPAR{gamma} activity, highlighting an important novel role of intracellular adiponectin.

physiology↗

bioRxiv2023

Loss of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids and Drives Sexually Dimorphic Liver Disease in Mice

Background and AimsGenome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the impact by which liver-specific CPT1a deletion impacts hepatic lipid metabolism. Approach and ResultsSix-to-eight-week old male and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (HFD; 60% kcal fat) for 15 weeks. Mice were necropsied after a 16 hour fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine aminotransferase (ALT) levels which were associated with greater deposition of hepatic lipids, while male mice were not affected by CPT1a deletion relative to male control mice. Mice with CPT1a deletion had reductions in DHA-containing phospholipids at the expense of monounsaturated fatty acids (MUFA)-containing phospholipids in both whole liver and at the level of the lipid droplet (LD). Male and female LKO mice increased RNA levels of genes involved in LD lipolysis (Plin2, Cidec, G0S2) and in polyunsaturated fatty acid (PUFA) metabolism (Elovl5, Fads1, Elovl2), while only female LKO mice increased genes involved in inflammation (Ly6d, Mmp12, Cxcl2). Kinase profiling showed decreased protein kinase A (PKA) activity, which coincided with increased PLIN2, PLIN5, and G0S2 protein levels and decreased triglyceride hydrolysis in LKO mice. ConclusionsLiver-specific deletion of CPT1a promotes sexually dimorphic steatotic liver disease (SLD) in mice, and here we have identified new mechanisms by which females are protected from HFD-induced liver injury. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/553705v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@f42ea0org.highwire.dtl.DTLVardef@12135f2org.highwire.dtl.DTLVardef@15cd9d0org.highwire.dtl.DTLVardef@e0106b_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗