Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders.

Intensive farming of livestock along with recent food scandals and consumer deception have increased awareness about risks for human nutrition. In parallel, the demand for meat obtained under more natural conditions from animals that can freely forage has largely increased. Interestingly, the consumption of game meat has not become more common despite its excellent quality and content of polyunsaturated fatty acids (PUFAs). We addressed the question if game meat fatty acid composition is modified through kitchen preparation. By analysing muscle fatty acid (FA) composition (polar and total lipids) of five European game species in a raw and a processed state, we aimed to quantify the proportion of PUFA that are oxidised and hydrogenated during processing. All game meat species originated from local hunters and free-living individuals. To mimic a realistic situation a professional chef prepared the meat samples with gentle use of heat in a standardised way. Expectedly, the overall content of polyunsaturated fatty acids declined during the cooking process but the decrease size was <5% and the nutritiously most important n-3/n-6 ratio was not affected by processing (F1,54 = 0.46; p = 0.5). Generally, our samples contained species-specific high PUFA and n-3 FA contents but we point out that differentiating between species is necessary. Game meat thus provides a healthy meat source, as cooking does not substantially alter its favourable fatty acid composition. Further research is needed to elucidate species-specific differences and the role of habitat quality and locomotion for tissue composition.

Inflammatory bowel disease (IBD) represents a significant challenge to global health, characterized by intestinal inflammation, impaired barrier function, and dysbiosis, with limited therapeutic options. In this study, we isolated a novel strain of Bacillus subtilis (B. subtilis) and observed promising effects in protecting against disruption of the gut barrier. Our findings indicate that the enhancement of intestinal barrier function is primarily attributed to its metabolites. We identified a novel metabolite, 2‐hydroxy‐4‐methylpentanoic acid (HMP), derived from B. subtilis, that significantly improved intestinal barrier function. We also show that growth arrest and DNA damage 45A (GADD45A) is a key regulator of mucosal barrier integrity, which is activated by HMP and subsequently activates the downstream Wnt/β‐catenin pathway. Our findings potentially contribute to the development of probiotics‐derived metabolites or targeted “postbiotics” as novel therapeutics for the treatment or prevention of IBD and other diseases associated with intestinal barrier dysfunction.

Background: Skeletal muscle fat infiltration is a common feature during ageing, obesity and several myopathies associated with muscular dysfunction and sarcopenia. However, the regulatory mechanisms of intramuscular adipogenesis and strategies to reduce fat infiltration in muscle remain unclear. Here, we identified the growth arrest and DNA damage‐inducible alpha (GADD45A), a stress‐inducible histone folding protein, as a critical regulator of intramuscular fat (IMAT) infiltration.Methods: To explore the role of GADD45A on IMAT infiltration and muscle regeneration, the gain or loss function of GADD45A in intramuscular preadipocytes was performed. The adipocyte‐specific GADD45A knock‐in (KI) mice and high IMAT‐infiltrated muscle model by glycerol injection (50 μL of 50% v/v GLY) were generated. RNA‐sequencing, histological changes, gene expression, lipid metabolism, mitochondrial function and the effect of dietary factor epigallocatechin‐3‐gallate (EGCG) treatment (100 mg/kg) on IMAT infiltration were studied.Results: The unbiased transcriptomics data analysis indicated that GADD45A expression positively correlates with IMAT infiltration and muscle metabolic disorders in humans (correlation: young vs. aged people, Gadd45a and Cebpa, r² = 0.20, P < 0.05) and animals (correlation: wild‐type [WT] vs. mdx mice, Gadd45a and Cebpa, r² = 0.38, P < 0.05; NaCl vs. GLY mice, Gadd45a and Adipoq/Fabp4, r² = 0.80/0.71, both P < 0.0001). In vitro, GADD45A overexpression promotes intramuscular preadipocyte adipogenesis, upregulating the expression of adipogenic genes (Ppara: +47%, Adipoq: +28%, P < 0.001; Cebpa: +135%, Fabp4: +16%, P < 0.01; Pparg: +66%, Leptin: +77%, P < 0.05). GADD45A knockdown robustly decreased lipid accumulation (Pparg: −57%, Adipoq: −35%, P < 0.001; Fabp4: −37%, P < 0.01; Leptin: −28%, P < 0.05). GADD45A KI mice exhibit inhibited skeletal muscle regeneration (myofibres: −40%, P < 0.01) and enhanced IMAT infiltration (adipocytes: +20%, P < 0.05). These KI mice have impaired exercise endurance and mitochondrial function. Mechanistically, GADD45A affects ATP synthase F1 subunit alpha (ATP5A1) ubiquitination degradation (ubiquitinated ATP5A1, P < 0.001) by recruiting the E3 ubiquitin ligase TRIM25, which decreases ATP synthesis (ATP production: −23%, P < 0.01) and inactivates the cAMP/PKA/LKB1 signalling pathway (cAMP: −36%, P < 0.01; decreased phospho‐PKA and phospho‐LKB1 protein content, P < 0.01). The dietary factor EGCG can protect against muscle fat infiltration (triglyceride: −64%, P < 0.05) via downregulating GADD45A (decreased GADD45A protein content, P < 0.001).Conclusions: Our findings reveal a crucial role of GADD45A in regulating muscle repair and fat infiltration and suggest that inhibition of GADD45A by EGCG might be a potential strategy to combat fat infiltration and its associated muscle dysfunction.

SUMMARY: It has been suggested that maximum sustained metabolic rate (SusMR) in mammals as reached, for instance, during lactation, is due to a limited capacity for heat dissipation. Here, we experimentally tested whether heat dissipation limitation (HDL) also constrains energy turnover in lactating European hares. Experimentally, we made use of the fact that hares nurse their young only once per day, which allowed us to keep females and young either at the same or at different ambient temperatures. During the last lactation week (week 4) females kept at thermoneutrality (22°C), irrespective of the cold load of their young, had significantly lower rates of metabolisable energy intake (MEI) than cold-exposed mothers (5°C), as predicted by the HDL hypothesis. However, in week 2 of lactation females at thermoneutrality rearing cold-exposed young were able to increase MEI to levels indistinguishable from those of cold-exposed females. Thus, even at thermoneutral temperature females reached maximum rates of energy turnover, which was inconsistent with the HDL hypothesis. We conclude that SusMR in lactating European hares typically results not from physiological constraints but from an active restriction of their energy turnover in order to maximise lifetime reproductive success.