Biology subjects

Neess, D.

Publications and source records attributed to Neess, D..

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

Acyl-CoA Binding Protein is Dispensable for White and Brown Adipose Tissue Function

Acyl-CoA binding protein (ACBP) plays a vital role in lipid metabolism by mediating the intracellular flux and utilization of long-chain acyl-CoAs. In this study we generated brown- and white adipose tissue specific knockout mice (Adipoq-Acbp-/-) and brown adipose tissue specific knockout mice (Ucp1-Acbp-/-) to investigate the role of ACBP in adipose tissue function. Here we demonstrate that loss of ACBP does not affect body weight, fat and lean mass, food intake and systemic energy expenditure, even under cold stress. Transcriptomic data show only minor changes in gene expression, whereas lipidomic profiling reveals a subtle increase in acyl-carnitines levels in brown adipose tissue. However, lipolytic activity in white adipose tissue as well as plasma glycerol, non-esterified fatty acid and triacylglycerol levels remained unaffected. In addition, no changes in mitochondrial respiration in BAT were observed. Taken together, our findings suggest that ACBP is dispensable for adipose tissue function and systemic energy metabolism, including thermoregulation.

biochemistry↗

bioRxiv2020

The Epidermal Barrier is Indispensable for Systemic Energy Homeostasis

ObjectivesHomeostatic regulation of body temperature is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and neuronal regulators. Although the skin is the largest sensory organ of the human body, and plays a fundamental role in regulating body temperature, it is surprising that adaptive alterations in skin functions and morphology only vaguely have been associated with physiological responses to cold stress or sensation of ambient temperatures. MethodsTo unravel the physiological responses to a compromised epidermal barrier in detail we have used animal models with either defects in skin lipid metabolism (ACBP-/- and skin-specific ACBP-/- knockout mice) or defects in skin structural proteins (ma/ma Flgft/ft). The primary objective was to clarify how defects in epidermal barrier function affect 1) energy expenditure by indirect calorimetry, 2) response to high fat feeding and a high oral glucose load and 3) expression of brown-selective gene programs by quantitative PCR in inguinal WAT (iWAT). ResultsWe show that mice with a compromised epidermal barrier function exhibit increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, is reversed by housing the mice at thermoneutrality (30{degrees}C) or by pharmacological {beta}-adrenergic blocking. These findings show that a compromised epidermal barrier induces a {beta}-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature. ConclusionOur findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis. HighlightsEnergy expenditure is significantly augmented in mice with impaired epidermal barrier. Mice with compromised barrier display increased food intake while maintaining normal bodyweight. Mice with an impaired epidermal barrier are resistant to diet-induced obesity and insulin resistance. Compromised barrier function induces expression of brown-selective gene programs in iWAT. Thermoneutral housing or blocking {beta}-adrenergic signaling prevents induction of brite-selective genes in iWAT and reverses food intake.

biochemistry↗