Background Neonicotinoid pesticides, including acetamiprid (ACE), are widely used in agriculture and pose increasing concerns due to their persistence in the environment and potential human exposure mainly through diet. Available evidence suggests that ACE may disrupt adipocyte function and promote metabolic dysfunctions such as obesity; however, there is limited research on how ACE negatively affects adipose tissue (AT) in men and women. This study utilizes an ex vivo translational model to clarify the sex-specific effects of ACE on AT metabolic and inflammatory profile of a vulnerable human substrate, such as the visceral AT of subjects with severe obesity. Methods Twenty-four subjects with severe obesity (11 men and 13 women) undergoing bariatric surgery were recruited from St. Andrea University Hospital (Rome, Italy). Visceral adipose tissue biopsies were collected and either treated with ACE or left untreated for further gene and protein expression analysis by RT-qPCR and Western blot, respectively. In addition, adipocytokines secretion, reactive oxygen species production, and free fatty acid release were measured in adipose tissue culture media using commercial or in house assays. Results Our findings demonstrate that ACE induces distinct sex-dependent alterations in lipid metabolism, Adipokines regulation, and inflammatory pathways. Specifically, it significantly lowers PPARγ gene expression but raises protein levels, particularly in men. Free fatty acid release increases and Hormone Sensitive Lipase (HSL) drops in both sexes, while Lipoprotein Lipase (LPL) decreases only in women. ACE also promotes inflammation mainly in women, increasing TNF-α, NF-κB, and reactive oxygen species. Conclusion These results show that the neonicotinoid ACE worsens AT dysfunction via inflammatory and metabolic pathways in a sex-specific way, likely leading to different risks of obesity-related complications. Overall, these findings provide a mechanistic basis for understanding the toxicological risk of neonicotinoids, highlighting the importance of sex-specific assessment in evaluating metabolic risks of environmental pesticide exposure.

MicroRNA-150 deficiency promotes progesterone synthesis and apoptosis in goat luteal cells by targeting nuclear receptor NR4A1.

Dietary Eucommia ulmoides leaf extract supplementation improves antioxidative status, meat quality, and structure of cecal microbiota in finishing pigs.

The circadian clock plays a critical role in coordinating energy metabolism across tissues, including brown adipose tissue (BAT), a major site of nonshivering thermogenesis. This study aimed to elucidate the cell-autonomous role of the peripheral circadian clock in brown adipocyte thermogenesis using an in vitro model independent of extrinsic cues. Primary brown adipocytes were differentiated from the stromal vascular fraction of interscapular BAT isolated from C57BL/6J mice. An in vitro model of BAT clock disruption was established by siRNA-mediated knockdown of the core clock gene Bmal1. Thermogenic function was assessed via measurement of oxygen consumption rate (OCR) using an extracellular flux analyzer. To further assess the thermogenic process, protein expression levels of lipolytic enzymes and mitochondrial oxidative phosphorylation (OXPHOS) complexes were analyzed by Western blotting. Bmal1-knockdown markedly reduced both basal and β-adrenergic-stimulated OCR, indicating impaired thermogenic function, despite comparable cellular differentiation, preserved β-adrenergic responsiveness, and elevated uncoupling protein 1 (Ucp1) expression. Notably, Bmal1-deficient cells exhibited decreased protein expression of key lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), as well as multiple mitochondrial oxidative phosphorylation (OXPHOS) subunits, suggesting decreased free fatty acid supply and reduced mitochondrial ability to generate the proton gradient required for UCP1-mediated thermogenesis. The peripheral circadian clock in brown adipocytes supports thermogenic function by regulating lipid mobilization and mitochondrial oxidative function, thus its disruption may lead to decreased energy expenditure and increased susceptibility to metabolic disorders.

Lipid droplets (LDs) are dynamic organelles that extend beyond lipid storage to regulate diverse aspects of reproductive physiology. In both mammals and Caenorhabditis elegans, LDs support gamete maturation, fertilization, embryogenesis and steroidogenesis by modulating lipid mobilization, signaling pathways, protein quality control and hormone production. The present review highlights the roles of LDs in oocytes, sperm, Sertoli and granulosa cells, embryonic stem cells and early embryos. Key regulatory molecules, including perilipins, adipose triglyceride lipase, Hormone‑Sensitive Lipase (HSL), Diacylglycerol O‑acyltransferases and seipin, as well as lipophagy, are discussed in the context of reproductive cell function. C. elegans demonstrates conserved genetic pathways linking LD metabolism with gamete quality and embryonic viability. The present review aimed to discuss emerging technologies such as lipidomics, high‑resolution imaging, Clustered Regularly Interspaced Short Palindromic Repeats screening and single‑cell sequencing that enable deeper investigation into LD dynamics. Finally, the present review aimed to examine how LD dysfunction contributes to reproductive disorders including infertility, polycystic ovary syndrome and metabolic syndrome. Understanding LD biology offers promising avenues for improving reproductive health and gamete and embryonic developmental potential.

ABSTRACT Fever reflects a physiological rise in body temperature accompanied by elevated production of adrenaline. The increased body temperature in fever is caused by shivering thermogenesis in skeletal muscle and non-shivering thermogenesis in brown adipose tissue (BAT), the latter being mediated by uncoupled oxidation of free fatty acids (FFAs). We hypothesized that an acute temperature rise to 40°C increases adrenalin-induced lipolysis in white adipocytes, thereby potentially providing FFAs as an energy substrate to sustain fever-induced thermogenesis in skeletal muscle and BAT. In 3T3-L1 and primary murine white adipocytes, isoproterenol-induced extracellular FFA accumulation was significantly increased at 40°C compared to 37°C. In contrast, isoproterenol-induced increase in extracellular glycerol concentrations and the protein levels of phosphorylated hormone sensitive lipase were comparable at both temperatures, suggesting a similar degree of lipolysis. Moreover, incubation at 40°C did neither increase isoproterenol-induced oxygen consumption nor intracellular FFA concentrations, indicating that the elevated extracellular FFA accumulation was not due to reduced intracellular consumption. Conversely, isoproterenol blunted FFA uptake into adipocytes to a significantly higher extent at 40°C compared to 37°C. Hence, an acute temperature rise to 40°C reduces FFA uptake into white adipocytes, thereby increasing extracellular FFA availability.

Effects of acute high-temperature stress on respiratory metabolism, tissue structure, and glycolipid metabolism in subadult Procambarusclarkii.

Exposure to hypoxic environments leads to neurological dysfunction, with recent studies implicating microglia-derived neuroinflammation involved in hypoxia-induced neuronal impairment. However, the underlying pathological mechanisms remain largely unclear. Lipid-droplet-accumulating microglia(LDAM) have been linked to age-related and genetic formsofneurodegeneration, prompting the investigation of their role in hypoxia-induced neuronal impairment. In this study, we observed that hypoxia induced lipid droplets accumulation in microglia, accompanied by increased levels of RETSAT, an enzyme involved in lipid metabolism regulation. Conditional knockout of RETSAT in microglia decreased lipid dropletsaccumulation and alleviates hypoxia-induced microglial-derived neuroinflammation and oxidative stress, both invitro and invivo. Our biological studies indicate that the beneficial effects of RETSAT knockout on lipid droplets degradation areprimarily mediated through enhanced activity of hormone-sensitive lipase (HSL). Furthermore, we found that the hypoxicadaptation-related RETSAT mutation Q247R promotes microglia lipolysis under hypoxic conditions. These findings suggest that RetSat is a potential therapeutic target for the prevention and treatment of hypoxia-induced microglial activation.

Short-term exposure to lauric acid promotes adipose tissue lipolysis and reduces leptin expression via a PPARγ-dependent mechanism.

IntroductionLipodystrophy is a rare and heterogeneous disorder characterized by selective loss or abnormal redistribution of adipose tissue, leading to metabolic complications such as insulin resistance, diabetes mellitus, hepatic steatosis, and dyslipidemia. Lipodystrophy is divided into 4 main groups: congenital generalized lipodystrophy (CGL), familial partial lipodystrophy (FPLD), acquired generalized lipodystrophy (AGL), and acquired partial lipodystrophy (APL). FPLD is caused by mutations is genes regulating adipocyte function and lipid metabolism, with six subtypes identified to date. Among these, type 6 (FPLD6) results from inactivating mutation in the LIPE gene, which encodes hormone-sensitive lipase (HSL). Here, we present a very rare case of autosomal recessive familial partial lipodystrophy type 6.Clinical CaseA 34-year-old female was referred for evaluation of suspected Cushing’s syndrome. She was receiving hormone replacement therapy for primary ovarian insufficiency and had no other known medical conditions. She had gestational diabetes during her second pregnancy, managed with diet alone. Over three years she gained 29 kg (BMI 35.2 kg/m²). Family history revealed parental consanguinity. Physical examination revealed characteristic cushingoid features including a prominent buffalo hump, supraclavicular fat pads, and centripetal obesity. She had fat accumulation in the upper body while subcutaneous fat was markedly reduced in the extremities and breasts (Figure 1). Acanthosis nigricans was noted in the axillary and cervical regions. Additionally, she had undergone a cosmetic liposuction procedure targeting the deltoid and occipital regions. Low-dose dexamethasone testing excluded Cushing’s syndrome. Oral glucose tolerance test indicated insulin resistance; triglycerides were elevated, while leptin was normal. Laboratory results are summarized in Table 1. Whole-body DXA demonstrated markedly reduced fat mass in the upper and lower extremities, with central fat accumulation. This distribution was compatible with partial lipodystrophy. FibroScan revealed advanced hepatic steatosis (S3) without fibrosis (F0), consistent with nonalcoholic fatty liver disease (NAFLD). Genetic analysis identified a homozygous pathogenic LIPE gene variant (c.2182G>A), confirming the diagnosis of autosomal recessive familial partial lipodystrophy type 6. Treatment with metformin, SGLT-2 inhibitor, and fenofibrate was initiated, alongside lifestyle modification and genetic counseling.ConclusionFPLD6 is a very rare subtype of familial partial lipodystrophy. Unlike other subtypes, it is caused by LIPE mutations leading to defective lipolysis, and typically presents in adulthood rather than early life. It is further characterized by severe insulin resistance, dyslipidemia, and hepatic steatosis. In addition, the presence of subcutaneous lipomas distinguishes FPLD6 from other many forms and may lead to diagnostic confusion with multiple lipomatosis.Figure 1:a.Sagittal magnetic resonance imaging (MRI) of the neck and cervical spine region demonstrating abnormal fat distribution consistent with partial lipodystrophy b.Dual-energy X-ray absorptiometry (DEXA) scan demonstrating body composition c.Posterior view of the trunk showing loss of peripheral fat and abnormal fat deposition in the upper body Table 1:Biochemical parameters of the patientIR: insulin resistance

Protein kinase C epsilon deletion in AgRP neurons modulates hypothalamic glucose sensing and improves glucose tolerance in mice

Hormone-sensitive lipase drives pro-resolving macrophage polarization and enhances efferocytosis

Cyclic guanosine monophosphate (cGMP) improves freezing tolerance of sheep embryos by reducing lipid content.

Aerobic exercise attenuates intramyocellular lipid accumulation by upregulating vitamin D receptor.

RSK2 facilitates beige fat formation through thermogenic and glycolytic pathways.

Obesity is a chronic metabolic inflammatory disease caused by energy excess, characterized by excessive adipose tissue accumulation, and is often accompanied by multiple complications such as type 2 diabetes mellitus, metabolic-associated fatty liver disease (MAFLD), and neurological disorders. Adipose tissue plays a central role in maintaining energy homeostasis. Under conditions of energy excess, pro-inflammatory M1-type adipose tissue macrophages (ATMs) are activated, secrete inflammatory factors, inhibit lipolysis and thermogenesis pathways, and exacerbate metabolic disorders. Insulin-like growth factor 2 (IGF2) possesses both metabolic and immunomodulatory functions and is associated with obesity risk; however, its role in ATM polarization remains unclear. This study aims to clarify the regulatory role and mechanism of IGF2 in obesity-related metabolic inflammation and cognitive function. A high-fat diet (HFD)-induced obese mouse model was established, and interventions were performed via intraperitoneal injection of recombinant IGF2 (rIGF2). Phenotypic polarization of ATMs and expression of inflammatory factors were analyzed by quantitative polymerase chain reaction (qPCR) and immunofluorescence staining. Western blotting was used to detect the expression levels of key proteins in the adrenergic signaling pathway and molecules related to lipolysis/thermogenesis in adipose tissue. Changes in the expression of hippocampal synaptic proteins and cognitive function were evaluated by Western blotting and cognition-related behavioral tests. The study found that rIGF2 intervention significantly promoted the polarization of ATMs from the pro-inflammatory M1 type to the anti-inflammatory M2 type, reduced the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), thereby relieving the inhibition of the β-adrenergic signaling pathway, activating the expression of hormone-sensitive lipase (HSL) and uncoupling protein 1 (UCP1), promoting lipolysis and thermogenesis, and effectively improving metabolic abnormalities such as insulin resistance and hepatic steatosis in obese mice. Meanwhile, rIGF2 treatment upregulated the expression of synaptic proteins (e.g., PSD-95, Synapsin-1) in the hippocampus of obese mice and significantly ameliorated HFD-induced cognitive impairment. This study is the first to systematically clarify the dual mechanism of IGF2 in regulating ATM polarization to improve metabolic inflammation, lipolysis-thermogenesis balance, and central cognitive impairment in obesity. The results suggest that IGF2 is not only a key regulator of energy metabolism but also possesses immunomodulatory and neuroprotective potential, providing a new theoretical basis and potential therapeutic target for the prevention and treatment of obesity and its related complications.

Nonalcoholic fatty liver disease (NAFLD) is commonly associated with overweight and obesity. But an increasing number of cases involve lean individuals, who tend to experience worse liver outcomes. In this study, we established mouse models of both obese and lean NAFLD by feeding mice a Western diet (WD) adlibitum and a WD with 30% caloric restriction (CR), respectively, to investigate the effects of piperine. After 12 weeks, hepatocyte lipid deposition and liver injury were similar in lean and obese NAFLD mice. Piperine treatment significantly reduced serum ALT levels and hepatic triglyceride (TG) content, alleviating hepatic steatosis in both groups. The mechanism of action involved the downregulation of fatty acid uptake, as evidenced by reduced expression of PPARγ and CD36, as well as the promotion of lipolysis through upregulation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). Additionally, piperine enhanced hepatic mitochondrial β-oxidation in the obese NAFLD model by upregulating carnitine palmitoyltransferase 1A (CPT1A). In conclusion, feeding a WD with 30% CR successfully induced lean NAFLD in mice, and piperine effectively alleviated NAFLD in both lean and obese mice.

Extracellular vesicles (EVs) derived from probiotic bacteria have recently emerged as postbiotic mediators that regulate host cellular responses. This study investigated the effects of EVs from Lactobacillus rhamnosus BS-Pro-08, isolated from kefir grains (Lacto EV), on adipocyte differentiation and lipid metabolism. Lacto EV treatment markedly suppressed the differentiation of 3T3-L1 preadipocytes into mature adipocytes, as reflected by reduced lipid accumulation and decreased expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). This inhibitory effect was most pronounced at the early stage of adipogenesis. In mature adipocytes, Lacto EV enhanced lipolysis in a dose-dependent manner, accompanied by increased glycerol release and total lipase activity. Interestingly, these lipolytic responses occurred despite reduced protein levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), suggesting that Lacto EVs may mediate an EV-enhanced lipolysis that is not fully explained by canonical ATGL/HSL signaling. Collectively, these findings demonstrate that Lacto EV modulates both adipogenic and lipolytic processes in vitro, providing insight into the metabolic actions of probiotic-derived vesicles.

Background: Korean red ginseng marc (KRGM), a by-product of Korean red ginseng (KRG) processing, retains numerous bioactive compounds with potential health benefits. Among them, KRGM-derived gintonin (KRGM-gintonin) is particularly rich in lysophosphatidic acid (LPA) and phospholipids, which have been linked to favorable metabolic effects. This study investigated the anti-obesity potential of KRGM-gintonin in high-fat diet (HFD)-induced obese mice, focusing on its impact on weight regulation, liver health, and energy metabolism. Methods: Obese mice (C57BL/6N, 4 weeks, male) were administered KRGM-gintonin either orally for 25 weeks or through intracerebroventricular (ICV) injection for 14 weeks. Throughout the study, body weight, food intake, metabolic parameters, liver tissue morphology, behavioral performance, and thermogenic gene expression were carefully monitored to evaluate treatment effects. Results: Both oral and ICV administration of KRGM-gintonin significantly reduced body weight gain in HFD-fed obese mice without altering food intake, suggesting enhanced energy expenditure. Treatment through both routes improved physical performance and increased metabolic rate. Oral KRGM-gintonin also alleviated fatty liver, reduced plasma triacylglycerol and cholesterol levels, and promoted the expression of thermogenesis-related genes, including uncoupling protein-1 (UCP1) and hormone-sensitive lipase (HSL), specifically in brown adipose tissue. Additionally, oral administration lowered tumor necrosis factor-α (TNF-α) expression, indicating anti-inflammatory activity and further supporting metabolic health. Conclusions: KRGM-gintonin exerts strong anti-obesity effects, primarily through oral administration, with supportive evidence from central ICV action. These findings highlight its potential as a functional therapeutic agent for obesity prevention and management, offering dual benefits in metabolic regulation and inflammation control.

Excessive lipolysis and inflammatory response in adipose tissue are associated with elevated serum growth hormone in dairy cows with clinical ketosis.