The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body\'s energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.

Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs). Neuronal p53 transactivated the promoter of microRNA-183 (miR-183) cluster, thereby upregulating biogenesis of miR-183-5p (miR-183), miR-96-5p (miR-96), and miR-182-5p. Both miR-183 and miR-96 directly targeted and post-transcriptionally suppressed VDACs. Neuronal ablation of p53 protected against ATP deficiency and neurological deficits, whereas post-stroke rescue of miR-183/VDAC signaling reversed these benefits. Interestingly, cyclin-dependent kinase 9 (CDK9) was found to be enriched in cortical neurons and upregulated the p53-induced transcription of the miR-183 cluster in neurons after ischemia. Post-treatment with the CDK9 inhibitor oroxylin A promoted neuronal ATP production mainly through suppressing the miR-183 cluster/VDAC axis, further improved long-term sensorimotor abilities and spatial memory, and alleviated depressive-like behaviors in mice following stroke. Our findings reveal an intrinsic CDK9/p53/VDAC pathway that drives neuronal bioenergy decline and underlies post-stroke cognitive impairment and depression, thus highlighting the therapeutic potential of oroxylin A for better outcomes.

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Traditional Chinese medical literature contains numerous records of many traditional Chinese herbal medicines that exhibit efficacy in enhancing resistance to cold, yet there is a lack of scientific explanation. Lycium barbarum is among the herbal medicines that are explicitly documented to enhance resistance to cold in the \"Ben Cao Gang Mu (Compendium of Materia Medica)\". Herein, we investigated L. barbarum polysaccharide (LBP)-induced browning of inguinal white adipose tissue (iWAT), energy expenditure and thermogenic function in a long-term (4 months) treatment mouse model. LBP supplementation resulted in a significant reduction in weight and adipocyte size in iWAT, along with increased gut microbiota diversity. Specifically, the levels of Lachnospiraceae, Ruminococcaceae and Bacteroidaceae (short-chain fatty acid-producing bacteria) were elevated, leading to a higher level of short-chain fatty acids (SCFAs) in the caecal content. These effects subsequently triggered the release of glucagon-like peptide-1 (GLP-1) and activated the CREB/PGC1α signaling pathway in iWAT, thereby increasing energy expenditure and enhancing thermogenic function. The antibiotic treatment experiments confirmed that the LBP-mediated gut microbiota participated in the process of iWAT browning. In summary, our findings provide the first scientific explanation and mechanistic insights into the cold resistance of L. barbarum and identify potentially safe natural product supplements for individuals in alpine areas.

Sortilin-related receptor 1 (SorL1) deficiency is a genetic predisposition to familial Alzheimer\'s disease (AD), but its pathology is poorly understood. In SorL1-null rats, a disorder of the global endosome-lysosome network (ELN) is found in hippocampal neurons. Deletion of amyloid precursor protein (APP) in SorL1-null rats could not completely rescue the neuronal abnormalities in the ELN of the hippocampus and the impairment of spatial memory in SorL1-null young rats. These in vivo observations indicated that APP is one of the cargoes of SorL1 in the regulation of the ELN, which affects hippocampal-dependent memory. When SorL1 is depleted, the endolysosome takes up more of the lysosome flux and damages lysosomal digestion, leading to pathological lysosomal storage and disturbance of cholesterol and iron homeostasis in the hippocampus. These disturbances disrupt the original homeostasis of the material-energy-subcellular structure and reprogram energy metabolism based on fatty acids in the SorL1-null hippocampus, instead of glucose. Although fatty acid oxidation increases ATP supply, it cannot reduce the levels of the harmful byproduct ROS during oxidative phosphorylation, as it does in glucose catabolism. Therefore, the SorL1-null rats exhibit hippocampal degeneration, and their spatial memory is impaired. Our research sheds light on the pathology of SorL1 deficiency in AD.

Obesity arises from an imbalance between energy consumption and energy expenditure, and thyroid hormone levels serve as a determinant of energy expenditure. We conducted experiments at the animal and cellular levels and combined those findings with clinical data to elucidate the role of triiodothyronine (T3) in facilitating the browning of white adipose tissue (WAT) and its underlying mechanism. The results showed (i) the impaired metabolic function of local WAT and the compensatory elevation of systemic thermogenesis in obesity; (ii) T3 treatment of white adipocytes in vitro and local WAT in vivo induced a shift towards a morphologically \"brown\" phenotype, accompanied by upregulation of mRNA and protein expression of browning-related and mitochondrial function markers, which suggest that T3 intervention promotes the browning of WAT; and (iii) the aforementioned processes could be modulated through inhibition of the PI3K/AKT signalling pathway; however, whether T3 affects the PI3K/AKT signalling pathway by affecting insulin signalling remains to be studied and clarified. The results of our study indicate that T3 treatment promotes browning of WAT through inhibition of the PI3K/AKT signalling pathway; these findings offer novel perspectives regarding the potential of localised therapies for addressing WAT volume in individuals with obesity.

The incidence of aging-related neurodegenerative disorders and neurocritical care diseases is increasing worldwide. Microglia, the main inflammatory cells in the brain, could be potential viable therapeutic targets for treating neurological diseases. Interestingly, mitochondrial functions, including energy metabolism, mitophagy and transfer, fission and fusion, and mitochondrial DNA expression, also change in activated microglia. Notably, mitochondria play an active and important role in the pathophysiology of neurodegenerative disorders and neurocritical care diseases. This review briefly summarizes the current knowledge on mitochondrial dysfunction in microglia in neurodegenerative disorders and neurocritical care diseases and comprehensively discusses the prospects of the application of neurological injury prevention and treatment targets by mitochondria.

Biofilm formation enhances bacterial survival and antibiotic tolerance, but the underlying mechanisms are incompletely understood. Here, we show that biofilm growth is accompanied by a reduction in bacterial energy metabolism and membrane potential, together with metabolic exchanges between the inner and outer regions in biofilms. More specifically, nutrient-starved cells in the interior supply amino acids to cells in the periphery, while peripheral cells experience a decrease in membrane potential and provide fatty acids to interior cells. Fatty acids facilitate the repair of starvation-induced membrane damage in inner cells and enhance their survival in the presence of antibiotics. Thus, metabolic exchanges between inner and outer cells contribute to survival of the nutrient-starved inner cells and contribute to antibiotic tolerance within the biofilm.

BACKGROUND: Evaluating energy expenditure is important for establishing optimal goals for nutrition treatment. However, indirect calorimetry, the reference standard for measuring energy expenditure, is difficult to apply widely in clinical practice.
OBJECTIVE: To test the consistency of bioelectrical impedance analysis (BIA) relative to indirect calorimetry for evaluating energy expenditure in critically ill patients.
METHODS: A cross-sectional study of 140 critically ill adult patients was conducted. Within 24 hours of a patient being transferred to the intensive care unit, trained researchers assessed the patient\'s energy expenditure by use of BIA and indirect calorimetry simultaneously. Consistency of the 2 measurements was detected by intraclass correlation coefficients with a 2-way random-effects model. Factors affecting consistency were analyzed.
RESULTS: Median energy expenditure measured by indirect calorimetry was 1430.0 kcal/d (IQR, 1190.5-1650.8 kcal/d). Median energy expenditure measured by BIA was 1407.0 kcal/d (IQR, 1248.5-1563.5 kcal/d). The correlation coefficient between indirect calorimetry and BIA was 0.813 (95% CI, 0.748-0.862; P < .001). The consistency of the 2 measurements was lower in patients with comorbidities than in those without (P = .004).
CONCLUSIONS: Results of BIA were highly consistent with indirect calorimetry assessments of energy expenditure in critically ill patients. Few factors except comorbidity affect the accuracy of BIA when assessing energy expenditure. Therefore, as a low-cost, easy-to-use, and noninvasive method, BIA is a valuable clinical tool for assessing energy expenditure in critically ill patients.

Global warming intensifies the water cycle, resulting in significant increases in precipitation and river runoff, which brings severe hypo-salinity stress to nearshore coral reefs. Ecological investigations have found that some corals exhibit remarkable adaptability to hypo-salinity stress during mass-bleaching events. However, the exact cause of this phenomenon remains unclear. To elucidate the potential molecular mechanism leading to high tolerance to hypo-salinity stress, Pocillopora damicornis was used as a research object in this study. We compared the differences in transcriptional responses and symbiotic microbiomes between bleaching and unbleaching P. damicornis during hypo-salinity stress caused by extreme pre-flood rainfall over South China in 2022. The results showed that: (1) Under hypo-salinity stress, the coral genes related to immune defense and cellular stress were significantly upregulated in bleaching corals, indicating more severe immune damage and stress, and the Symbiodiniaceae had no significant gene enrichment. Conversely, metabolic genes related to glycolysis/gluconeogenesis were significantly downregulated in unbleaching corals, whereas Symbiodiniaceae genes related to oxidative phosphorylation were significantly upregulated to meet the energy requirements of coral holobiont; (2) C1d was the dominant Symbiodiniaceae subclade in all samples, with no significant difference between the two groups; (3) The symbiotic bacterial community structure was reorganized under hypo-salinity stress. The abundance of opportunistic bacteria increased significantly in bleaching coral, whereas the relative abundance of probiotics was higher in unbleaching coral. This may be due to severe immune damage, making the coral more susceptible to opportunistic infection and bleaching. These results suggest that long-term hypo-salinity acclimation in the Pearl River Estuary enhances the tolerance of some corals to hypo-salinity stress. Corals with higher tolerance may reduce energy consumption by slowing down their metabolism, improve the energy metabolism of Symbiodiniaceae to meet the energy requirements of the coral holobiont, and alter the structure of symbiotic bacterial communities to avoid bleaching.