Proto-oncogene FAM83A contributes to casein kinase 1-mediated mitochondrial maintenance and white adipocyte differentiation.

Family with sequence similarity 83 A (FAM83A) is a newly discovered proto-oncogene that has been shown to play key roles in various cancers. However, the function of FAM83A in other physiological processes is not well known. Here, we report a novel function of FAM83A in adipocyte differentiation. We used an adipocyte-targeting fusion oligopeptide (FITC-ATS-9R) to deliver a FAM83A-sgRNA/Cas9 plasmid to knockdown Fam83a (ATS/sg-FAM83A) in white adipose tissue in mice, which resulted in reduced white adipose tissue mass, smaller adipocytes, and mitochondrial damage that was aggravated by a high-fat diet. In cultured 3T3-L1 adipocytes, we found loss or knockdown of Fam83a significantly repressed lipid droplet formation and downregulated the expression of lipogenic genes and proteins. Furthermore, inhibition of Fam83a decreased mitochondrial ATP production through blockage of the electron transport chain, associated with enhanced apoptosis. Mechanistically, we demonstrate FAM83A interacts with casein kinase 1 (CK1) and promotes the permeability of the mitochondrial outer membrane. Furthermore, loss of Fam83a in adipocytes hampered the formation of the TOM40 complex and impeded CK1-driven lipogenesis. Taken together, these results establish FAM83A as a critical regulator of mitochondria maintenance during adipogenesis.

The microbiota-gut-brain axis: A novel nutritional therapeutic target for growth retardation.

Growth retardation (GR), which commonly occurs in childhood, is a major health concern globally. However, the specific mechanism remains unclear. It has been increasingly recognized that changes in the gut microbiota may lead to GR through affecting the microbiota-gut-brain axis. Microbiota interacts with multiple factors such as birth to affect the growth of individuals. Microbiota communicates with the nerve system through chemical signaling (direct entry into the circulation system or stimulation of enteroendocrine cells) and nervous signaling (interaction with enteric nerve system and vagus nerve), which modulates appetite and immune response. Besides, they may also influence the function of enteric glial cells or lymphocytes and levels of systemic inflammatory cytokines. Environmental stress may cause leaky gut through perturbing the hypothalamic-pituitary-adrenal axis to further result in GR. Nutritional therapies involving probiotics and pre-/postbiotics are being investigated for helping the patients to overcome GR. In this review, we summarize the role of microbiota in GR with human and animal models. Then, existing and potential regulatory mechanisms are reviewed, especially the effect of microbiota-gut-brain axis. Finally, we propose nutritional therapeutic strategies for GR by the intervention of microbiota-gut-brain axis, which may provide novel perspectives for the treatment of GR in humans and animals.

Zfp217 mediates m6A mRNA methylation to orchestrate transcriptional and post-transcriptional regulation to promote adipogenic differentiation.

A complex and highly orchestrated gene expression program chiefly establishes the properties that define the adipocyte phenotype, in which the vast majority of factors are involved in transcriptional regulation. However, the mechanisms by post-transcriptional modulation are poorly understood. Here, we showed that zinc finger protein (Zfp217) couples gene transcription to m6A mRNA modification to facilitate adipogenesis. Zfp217 modulates m6A mRNA methylation by activating the transcription of m6A demethylase FTO. Consistently, depletion of Zfp217 compromises adipogenic differentiation of 3T3L1 cells and results in a global increase of m6A modification. Moreover, the interaction of Zfp217 with YTHDF2 is critical for allowing FTO to maintain its interaction with m6A sites on various mRNAs, as loss of Zfp217 leads to FTO decrease and augmented m6A levels. These findings highlight a role for Zfp217-dependent m6A modification to coordinate transcriptional and post-transcriptional regulation and thus promote adipogenic differentiation.

Transcriptome Profiling of m6A mRNA Modification in Bovine Mammary Epithelial Cells Treated with Escherichia coli.

Mastitis is a common disease in dairy cows that is mostly caused by E. coli, and it brings massive losses to the dairy industry. N6-Methyladenosine (m6A), a methylation at the N6 position of RNA adenine, is a type of modification strongly associated with many diseases. However, the role of m6A in mastitis has not been investigated. In this study, we used MeRIP-seq to sequence the RNA of bovine mammary epithelial cells treated with inactivated E. coli for 24 h. In this in vitro infection model, there were 16,691 m6A peaks within 7066 mRNA transcripts in the Con group and 10,029 peaks within 4891 transcripts in the E. coli group. Compared with the Con group, 474 mRNAs were hypermethylated and 2101 mRNAs were hypomethylated in the E. coli group. Biological function analyses revealed differential m6A-modified genes mainly enriched in the MAPK, NF-κB, and TGF-ß signaling pathways. In order to explore the relationship between m6A and mRNA expression, combined MeRIP-seq and mRNA-seq analyses revealed 212 genes with concomitant changes in the mRNA expression and m6A modification. This study is the first to present a map of RNA m6A modification in mastitis treated with E. coli, providing a basis for future research.

Adipocyte dedifferentiation in health and diseases.

Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedifferentiation, whereby a mature adipocyte is reverted to an undifferentiated progenitor-like status, has been reported as a mechanism underlying adipocyte plasticity. Dedifferentiation of mature adipocytes has been observed under both physiological and pathological conditions. This review covers several aspects of adipocyte dedifferentiation, its relevance to adipose tissue function, molecular pathways that drive dedifferentiation, and the potential of therapeutic targeting adipocyte dedifferentiation in human health and metabolic diseases.

miR-221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin-1 (SIRT1).

It is well known that obesity-induced white adipose tissue inflammation is an important reason for insulin-resistance and type 2 diabetes mellitus. Sirtuin-1 (SIRT1) is an important regulator of inflammtion response pathways in white adipose tissue. Here, we found that miR-221 negatively regulated SIRT1 in white adipose tissue during inflammation and HFD-induced obesity. MiR-221 is a putative oncogene which has been found overexpressed in a number of human tumors. Recently, it has also found that miR-221 was increased in obese adipose tissue and may be involved in inflammation and insulin-resistance. However the specific mechanism remains to be elucidated. In our present study, we found that overexpression of miR-221 decreased the protein abundance of SIRT1 and caused inflammation and insulin-resistance in differentiated 3T3-L1 cells. Conversely, miR-221 inhibition increased the protein levels, ameliorated inflammation, and improved insulin sensitivity. Moreover, inhibition of SIRT1 by EX527 significantly diminished the downregulation of the inflammation and insulin-resistance levels induced by the miR-221 inhibitor. In conclusion, our data suggest that miR-221 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity, at least in part, through suppressing SIRT1.

Maternal obesity aggravates the abnormality of porcine placenta by increasing N6-methyladenosine.

BACKGROUND: The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. OBJECTIVE: This study attempts to investigate the novel RNA modification N6-methyladenosine (m6A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy. SUBJECTS/METHODS: Forty four placentas from eight sows (backfat thickness ≥21 mm) were divided into four groups by piglet weight, with group1 being LBW group (<1.0 kg), group2 (1.0-1.4 kg), group3 (1.4-1.6 kg), and group4 (>1.6 kg) as the comparative groups of normal birth weight. QPCR was used to measure the mRNA levels of the genes and western blot was used to test the content of proteins. At the same time, LC-MS/MS method was built to test the content of m6A modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific m6A modification in the key genes. RESULTS: Compared with the comparative groups, the expression levels of PPARγ, VEGFA, ABHD5, and GPR120 in both mRNA and protein decreased noticeably in the LBW group. It was also observed that the density of the H&E stained vessels became attenuated in LBW group. Importantly, for the first time, the increased m6A levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of m6A) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of m6A. By using MeRIP-QPCR technology, the m6A modification in PPARγ, VEGFA, ABHD5, and GPR120, as well as FTO, was considerably enhanced in the placentas from LBW group. CONCLUSION: We infer that in maternity obesity, the higher m6A modification displayed in the genes related to placental development, lipid metabolism and angiogenesis may result in the down regulation of these genes, which could be associated with m6A demethylase FTO.

GPR120: a critical role in adipogenesis, inflammation, and energy metabolism in adipose tissue.

It is well known that adipose tissue has a critical role in the development of obesity and metabolic diseases and that adipose tissue acts as an endocrine organ to regulate lipid and glucose metabolism. Accumulating in the adipose tissue, fatty acids serve as a primary source of essential nutrients and act on intracellular and cell surface receptors to regulate biological events. G protein-coupled receptor 120 (GPR120) represents a promising target for the treatment of obesity-related metabolic disorders for its involvement in the regulation of adipogenesis, inflammation, glucose uptake, and insulin resistance. In this review, we summarize recent studies and advances regarding the systemic role of GPR120 in adipose tissue, including both white and brown adipocytes. We offer a new perspective by comparing the different roles in a variety of homeostatic processes from adipogenic development to adipocyte metabolism, and we also discuss the effects of natural and synthetic agonists that may be potential agents for the treatment of metabolic diseases.

Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.

Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-ß (TGF-ß) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 µg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 µg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 µg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy.

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCß-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCß-Ca2+-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

Molecular cloning, expression pattern analysis of porcine Rb1 gene and its regulatory roles during primary dedifferentiated fat cells adipogenic differentiation.

Adipocytes are the main constituent of adipose tissue and are considered to be a corner stone in the homeostatic control of whole body metabolism. Recent reports evidenced that retinoblastoma 1 (Rb1) gene plays an important role in fat development and adipogenesis in mice. Here, we cloned the partial cDNA sequences of the porcine Rb1 gene which contains the complete coding sequences (CDS) of 2820bp encoding a protein of 939 amino acids. Bioinformatic analysis revealed that the CDS of porcine Rb1 was highly identical with those of cattle, human and mice. The porcine Rb1 has three typical conserved structural domains, including Rb-A pocket domain, CYCLIN domain and C-terminus domain, and the phylogenetic tree indicates a closer genetic relationship with cattle and human. Tissue distribution analysis showed that Rb1 expression appeared to be ubiquitously in various tissues, being higher in heart, liver, muscle, and stomach. Furthermore, significant downregulation of Rb1 was found at the initial stage of dedifferentiated fat (DFAT) cells adipogenic differentiation. With the knockdown of the Rb1 expression by siRNA, the number of DFAT cells recruited to white rather than brown adipogenesis was promoted, and mRNA levels of adipogenic markers, such as PPARγ, aP2, LPL and adiponectin and protein expression of PPARγ and adiponectin were increased after hormone stimulation. The underlying mechanisms may be that knockdown of Rb1 promotes the mitotic clonal expansion and PPARγ expression by derepressing the transcriptional activity of E2F so as to facilitate the first steps of adipogenesis. In summary, we cloned and characterized an important negative regulator in adipogenic commitment of porcine DFAT cells.

Current understanding of the role of DDX21 in orchestrating gene expression in health and diseases.

RNA helicases are involved in almost all biological events, and the DDXs family is one of the largest subfamilies of RNA helicases. Recently, studies have reported that RNA helicase DDX21 is involved in several biological events, specifically in orchestrating gene expression. Hence, in this review, we provide a comprehensive overview of the function of DDX21 in health and diseases. In the genome, DDX21 contributes to genome stability by promoting DNA damage repair and resolving R-loops. It also facilitates transcriptional regulation by directly binding to promoter regions, interacting with transcription factors, and enhancing transcription through non-coding RNA. Moreover, DDX21 is involved in various RNA metabolism such as RNA processing, translation, and decay. Interestingly, the activity and function of DDX21 are regulated by post-translational modifications, which affect the localization and degradation of DDX21. Except for its role of RNA helicase, DDX21 also acts as a non-enzymatic function in unwinding RNA, regulating transcriptional modifications and promoting transcription. Next, we discuss the potential application of DDX21 as a clinical predictor for diseases, which may facilitate providing novel pharmacological targets for molecular therapy.

Time-restricted feeding relieves high temperature-induced impairment on meat quality by activating the Nrf2/HO-1 pathway, modification of muscle fiber composition, and enriching the polyunsaturated fatty acids in pigs.

To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle.

Effects of Fermented Navel Orange Pulp on Growth Performance, Carcass Characteristics, Meat Quality, Meat Nutritional Value, and Serum Biochemical Indicators of Finishing Tibetan Pigs.

In order to cope with the limited supply of feed for global animal production, there is a pressing need to explore alternative feed resources. Orange pulp, a by-product of agriculture and industry, has shown potential to positively or neutrally impact pig productive performance when included in their diet. However, there is a lack of research on the effects of fermented navel orange pulp (FNOP) on pig growth and productive performance. This study aimed to investigate the effects of FNOP as a dry matter substitute on pig's growth performance, carcass characteristics, meat quality, meat nutritional value, and serum biochemical indicators. The experiment involved 128 finishing Tibetan pigs, divided into four feed treatment groups, with varying levels (0%, 5%, 10% and 15%) of FNOP replacing dry matter in the basal diet. The results indicate that substituting 5% to 15% FNOP had no adverse effects on pig growth performance. However, at a 15% substitution rate, there was a decrease in serum growth hormone and IGF-1 levels, along with an increase in the feed-to-gain ratio. A 10% FNOP replacement notably increased the loin-eye muscle area of pigs. Additionally, 5% and 10% FNOP substitutions reduced the drip loss of pork. The study also found that substituting 5% to 15% FNOP increased unsaturated fatty acids and umami nucleotide contents in pork and raised serum total protein and uric acid (nucleotide-metabolism-related product) levels. These findings suggest that moderate FNOP substitution might improve meat quality, nutritional value, and maintain growth and productive performance in Tibetan pigs by improving protein synthesis and nucleotide metabolism, while also reducing feed costs. The optimal substitution ratio identified was 10%.

Clostridium butyricum and carbohydrate active enzymes contribute to the reduced fat deposition in pigs.

Pig gastrointestinal tracts harbor a heterogeneous and dynamic ecosystem populated with trillions of microbes, enhancing the ability of the host to harvest energy from dietary carbohydrates and contributing to host adipogenesis and fatness. However, the microbial community structure and related mechanisms responsible for the differences between the fatty phenotypes and the lean phenotypes of the pigs remained to be comprehensively elucidated. Herein, we first found significant differences in microbial composition and potential functional capacity among different gut locations in Jinhua pigs with distinct fatness phenotypes. Second, we identified that Jinhua pigs with lower fatness exhibited higher levels of short-chain fatty acids in the colon, highlighting their enhanced carbohydrate fermentation capacity. Third, we explored the differences in expressed carbohydrate-active enzyme (CAZyme) in pigs, indicating their involvement in modulating fat storage. Notably, Clostridium butyricum might be a representative bacterial species from Jinhua pigs with lower fatness, and a significantly higher percentage of its genome was dedicated to CAZyme glycoside hydrolase family 13 (GH13). Finally, a subsequent mouse intervention study substantiated the beneficial effects of C. butyricum isolated from experimental pigs, suggesting that it may possess characteristics that promote the utilization of carbohydrates and hinder fat accumulation. Remarkably, when Jinhua pigs were administered C. butyricum, similar alterations in the gut microbiome and host fatness traits were observed, further supporting the potential role of C. butyricum in modulating fatness. Taken together, our findings reveal previously overlooked links between C. butyricum and CAZyme function, providing insight into the basic mechanisms that connect gut microbiome functions to host fatness.

Insights into the interplay between gut microbiota and lipid metabolism in the obesity management of canines and felines.

Obesity is a prevalent chronic disease that has significant negative impacts on humans and our companion animals, including dogs and cats. Obesity occurs with multiple comorbidities, such as diabetes, hypertension, heart disease and osteoarthritis in dogs and cats. A direct link between lipid metabolism dysregulation and obesity-associated diseases has been implicated. However, the understanding of such pathophysiology in companion animals is limited. This review aims to address the role of lipid metabolism in various metabolic disorders associated with obesity, emphasizing the involvement of the gut microbiota. Furthermore, we also discuss the management of obesity, including approaches like nutritional interventions, thus providing novel insights into obesity prevention and treatment for canines and felines.

Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.

Obesity represents a low-grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low-dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue-resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15-HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12-LOX) and 15- Hydroxyeicosatetraenoic acid (15-HETE) rescues the impaired thermogenesis. Interestingly, 15-HETE directly binds to AMP-activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15-HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity.

Phytosterols Protect against Osteoporosis by Regulating Gut Microbiota.

Osteoporosis is increasingly prevalent worldwide, representing a major health burden. However, there is a lack of nutritional strategies for osteoporotic therapy. Phytosterols, as natural bioactive compounds, have the potential to alleviate osteoporosis. In this study, a glucocorticoid-induced osteoporosis mouse model and treatment with low and high concentrations of phytosterols for 4 weeks were established. The results demonstrated that compared to the control group, low-concentration phytosterols (LP) (0.3 mg/mL) increased bone mass, improved trabecular microstructure, reduced serum levels of cross-linked C-telopeptide of type I collagen (CTX-1), and elevated serum levels of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Conversely, high-concentration phytosterols (0.5 mg/mL) showed no effect. Additionally, we validated the effect of LP in ameliorating osteoporosis using an ovariectomized (OVX)-induced osteoporosis mouse model. Mechanistically, phytosterols altered the microbial composition to counteract glucocorticoid-induced gut microbiota disorder and improve the length and morphology of the small intestine. Particularly, based on selection strategy and correlation analysis, phytosterols increased the relative abundance of Ruminococcus and decreased the relative abundance of Bilophila, which were significantly associated with glucocorticoid-induced osteoporosis indications. Overall, these findings suggest that phytosterols regulate gut microbiota to increase bone mass, thereby exerting an antiosteoporotic effect.

Effects of Dietary Phytosterol Supplementation on the Productive Performance, Egg Quality, Length of Small Intestine, and Tibia Quality in Aged Laying Hens.

This study aimed at investigating the effects of phytosterols on the productive performance, egg quality, length of small intestine, and tibia quality in aged laying hens. A total of 960 Dawu Jinfeng commercial laying hens (75 weeks of age) were randomly assigned to three groups. Each group had 16 replicates and every replicate contained four cages (five birds/cage). The control group hens received the basal diet without phytosterols. The hens in the experimental groups received a diet containing phytosterols at concentrations of 20 mg/kg and 40 mg/kg for 7 weeks. The results showed that phytosterols had a linearly increasing effect on egg weight, eggshell surface area, albumen height, and haugh unit at week 5 of experiment (p < 0.05). Supplemental phytosterols linearly and quadratically increased eggshell thickness (p < 0.05). At week 7 of the experiment, dietary supplementation of phytosterols linearly increased egg weight and eggshell weight (p < 0.05). Supplementation of 20 mg/kg, but not 40 mg/kg, phytosterols increased the length of the small intestine. However, dietary phytosterols had no effect on the laying rate, mortality, or liver index (p > 0.1). The results of tibia quality detected by micro-CT also showed no difference in the treatment of phytosterols. Therefore, supplementation with 20 mg/kg phytosterols in the diet improves egg quality and increases the length of small intestine, but has no effects on the quality of the tibia.

Lactate Conversion by Lactate Dehydrogenase B Is Involved in Beige Adipocyte Differentiation and Thermogenesis in Mice.

Adipose tissue (AT) is the primary reservoir of lipid, the major thermogenesis organ during cold exposure, and an important site for lactate production. However, the utilization of lactate as a metabolic substrate by adipocytes, as well as its potential involvement in the regulation of adipocyte thermogenesis, remain unappreciated. In vitro experiments using primary stromal vascular fraction preadipocytes isolated from mouse inguinal white adipose tissue (iWAT) revealed that lactate dehydrogenase B (LDHB), the key glycolytic enzyme that catalyzes the conversion of lactate to pyruvate, is upregulated during adipocyte differentiation, downregulated upon chronic cold stimulation, and regained after prolonged cold exposure. In addition, the global knockout of Ldhb significantly reduced the masses of iWAT and epididymal WAT (eWAT) and impeded the utilization of iWAT during cold exposure. In addition, Ldhb loss of function impaired the mitochondrial function of iWAT under cold conditions. Together, these findings uncover the involvement of LDHB in adipocyte differentiation and thermogenesis.