Circadian syndrome (CircS) combines metabolic abnormalities with short sleep and depressive symptoms. Whether dietary omega-6 polyunsaturated fatty acid subtypes have distinct associations with CircS remains unclear. We analyzed 11,459 adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 using survey-weighted logistic regression to examine dietary total omega-6 polyunsaturated fatty acids, linoleic acid (LA), and arachidonic acid (AA) in relation to CircS. Sensitivity analyses used energy-density exposures and additional adjustment for body mass index, red and processed meat intake, and diagnosis history. Complementary two-sample Mendelian randomization (MR) evaluated genetically predicted circulating omega-6-related traits against selected cardiometabolic and behavioral phenotypes; it did not directly test dietary AA or CircS. Total omega-6 polyunsaturated fatty acid and LA intake were not associated with CircS after full adjustment. Participants in the highest AA quartile had higher odds of CircS than those in the lowest quartile (odds ratio [OR] 1.41, 95
The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel inflammatory and metabolic biomarker, but its association with chronic obstructive pulmonary disease (COPD) in older adults remains unclear. This study investigated the relationship between UHR and COPD prevalence among adults aged ≥ 60 years. This cross-sectional study analyzed 5,277 participants aged ≥ 60 years from NHANES 2013–2018. Weighted multivariable logistic regression estimated the UHR–COPD association. Restricted cubic spline (RCS) analysis characterized the dose–response relationship, and receiver operating characteristic (ROC) curves evaluated model performance. Subgroup, sensitivity, and machine learning analyses were conducted. Variables with missingness of 20
Obesity has become a worldwide public health concern and is tightly associated with multiple metabolic complications. A dietary imbalance characterized by an elevated n-6/n-3 polyunsaturated fatty acid (PUFAs) ratio provokes systemic inflammation and exacerbates obesity-linked skeletal muscle atrophy. However, it remains incompletely understood whether the elevation of endogenous n-3 PUFAs protects against skeletal muscle homeostasis disruption. An obese mouse model was created by feeding mice with a HFD to examine the potential beneficial impacts of endogenous n-3 PUFAs on skeletal muscle health. Transgenic (TG) mice engineered to express an active Δ15 fatty acid desaturase (Δ15Des), an enzyme responsible for converting n-6 PUFAs to n-3 PUFAs, were used as the experimental group, and wild-type (WT) C57BL/6 mice served as the control group. All mice were assigned to three dietary regimens, including a normal diet (ND), an HFD, and an HFD supplemented with arachidonic acid (HFDA). After 12 weeks of intervention, various assessments were carried out. Distinct pathological alterations were observed in the gastrocnemius muscle of WT mice under HFD treatment. TG mice presented elevated n-3 PUFA levels, reduced n-6 PUFA levels, significantly decreased body weight (BW), less adipose tissue mass and lowered ectopic fat accumulation, along with better-preserved gastrocnemius muscle structure. Further analyses showed that obesity-induced skeletal muscle atrophy was ameliorated in TG mice. Reduced inflammation, decreased endoplasmic reticulum (ER) stress and mitochondrial autophagy markers, downregulated expression of muscle atrophy factors and upregulated expression of myogenic regulatory factors were also detected in TG mice. The expression of Δ15-desaturase in TG mice facilitates the endogenous conversion of long-chain n-6 PUFAs to n-3 PUFAs. This effect attenuates inflammation and ER stress, improves mitochondrial function, and alleviates obesity-related skeletal muscle atrophy. The findings provide a theoretical foundation for clinical interventions targeting fatty acid (FA) metabolism.
The demand for minimally invasive approaches to reduce localized adipose tissue has increased with the expansion of aesthetic medicine. To construct this review, a structured literature search (1990–2026) was conducted across PubMed, Scopus, and Web of Science. While injectable adipose reduction therapies have been used clinically for decades, their pharmacological mechanisms remain incompletely understood from an adipocyte biology perspective. Notably, it is critical to explicitly distinguish preclinical in vitro/in vivo evidence from human clinical trial data when evaluating these agents. Classical cytolytic agents, such as deoxycholic acid, reduce adipose tissue mainly through detergent-mediated membrane disruption and necrotic adipocyte death. Although these agents are strongly clinically validated, their efficacy relies on nonspecific membrane injury, local inflammation, and limited cellular selectivity. In contrast, metabolic and signaling-based agents (e.g., β-adrenergic agonists, phosphodiesterase inhibitors, and AMPK modulators) primarily regulate lipid mobilization and fatty acid oxidation without directly eliminating adipocytes. However, evidence supporting durable localized fat reduction with these approaches remains limited. Recent injectable agents represent a paradigm shift toward mechanism-defined adipocyte elimination. Preclinical evidence supporting the use of purified phosphatidylcholine-based formulations (e.g., AYP-101) suggests that purified phosphatidylcholine induces TLR4-associated NF-κB–TNF-α signaling, driving downstream lipolytic and apoptotic responses. Moreover, clinical reports of CBL-514 describe a proposed DYRK1B-linked apoptosis-oriented mechanism involving Bax/Bcl-2 regulation. Alternatively, RZL-012 represents a distinct liponecrotic approach involving direct membrane injury and inflammatory clearance. While apoptosis-oriented approaches may enable regulated adipocyte elimination, their comparative tissue selectivity requires further clinical validation. Furthermore, RNA-based interventions and adipose-targeted delivery systems are emerging as strategies to precisely regulate adipogenic and inflammatory pathways. This review critically compares major injectable strategies in terms of their pharmacological mechanisms, limitations, and translational potential. By reframing the field from simple fat volume reduction toward the regulation of adipocyte fate, lipid handling, and inflammatory remodeling, this framework supports the development of safer, mechanism-based therapies. Ultimately, these approaches may extend beyond aesthetic applications to the therapeutic modulation of dysfunctional adipose tissue in obesity. •Injectable adipose-reduction therapies differentially regulate adipocyte fate and tissue remodeling. •Detergent-based agents induce membrane disruption, necrosis, lipid release, and inflammation. •Metabolic modulators regulate lipid mobilization, oxidation, and fatty acid utilization. •Emerging agents encompass apoptosis-oriented and liponecrotic modes of adipocyte elimination. •Molecular targeting may improve tissue selectivity and support more precise adipose remodeling.
Limb-girdle muscular dystrophies (LGMD) are human genetic diseases resulting from defects in dysferlin, a membrane associated protein present in many cell types. LGMDs are characterised by marked deposition of lipids in affected muscles and eventual infiltration of adipocytes between myofibers. We have previously reported significant changes in the muscle lipidome in dysferlin-deficient mice, especially triglycerides, with concomitant increases in Dgat2, which encodes the protein that condenses diacylglycerol and fatty acyl-CoA to form triglyceride. The aim of this study was to determine the effect of DGAT2 inhibition in skeletal muscle on the progression of muscle wasting and pathology associated with dysferlinopathy. Dgat2 was inhibited in male BLA/J mice using skeletal muscle targeted adeno-associated virus delivery of a short hairpin RNA against Dgat2 (AAV-shRNA-Dgat2) prior to onset of myofiber adipose infiltration at 10 months of age. Measures of whole-body metabolism and functional ambulatory assessments were conducted 16–21 weeks after AAV administration, and skeletal muscle metabolism, muscle contractile function in situ and muscle histopathology were assessed at 23–26 weeks after AAV administration. AAV-shRNA-Dgat2 administration in BLA/J mice caused a mild reduction in body weight, whole-body fat mass and adipocyte infiltration within skeletal muscle. Indirect calorimetry analysis of metabolic efficiency revealed increased nighttime energy expenditure and decreased daytime activity in BLA/J mice treated with AAV-shRNA-Dgat2. Functional assessments showed Dgat2 inhibition in muscle improved balance, coordination and rearing in BLA/J mice. While inhibiting muscle adipocyte formation improved some metabolic parameters, AAV-shRNA-Dgat2 administration did not alter skeletal muscle contractile force generation in situ, muscle fatty acid metabolism, or regeneration after BaCl₂-induced injury. DGAT2 is a determinant of pathological adipocyte infiltration and ambulatory function in dysferlinopathy, thereby expanding the mechanistic framework linking lipid metabolism, muscle composition, and functional decline. Further work is required to understand the mechanistic basis that underpins this relationship.
