Metabolic diseases, featured with dysregulated energy homeostasis, have become major global health challenges. Patients with metabolic diseases have high probability to manifest multiple complications in lipid metabolism, e.g. obesity, insulin resistance and fatty liver. Therefore, targeting the hub genes in lipid metabolism may systemically ameliorate the metabolic diseases, along with the complications. Stearoyl-CoA desaturase 1(SCD1) is a key enzyme that desaturates the saturated fatty acids (SFAs) derived from de novo lipogenesis or diet to generate monounsaturated fatty acids (MUFAs). SCD1 maintains the metabolic and tissue homeostasis by responding to, and integrating the multiple layers of endogenous stimuli, which is mediated by the synthesized MUFAs. It critically regulates a myriad of physiological processes, including energy homeostasis, development, autophagy, tumorigenesis and inflammation. Aberrant transcriptional and epigenetic activation of SCD1 regulates AMPK/ACC, SIRT1/PGC1α, NcDase/Wnt, etc, and causes aberrant lipid accumulation, thereby promoting the progression of obesity, non-alcoholic fatty liver, diabetes and cancer. This review critically assesses the integrative mechanisms of the (patho)physiological functions of SCD1 in metabolic homeostasis, inflammation and autophagy. For translational perspective, potent SCD1 inhibitors have been developed to treat various types of cancer. We thus discuss the multidisciplinary advances that greatly accelerate the development of SCD1 new inhibitors. In conclusion, besides cancer treatment, SCD1 may serve as the promising target to combat multiple metabolic complications simultaneously.

Background: Taurine has been demonstrated to regulate and improve metabolic health. However, physiological and pathological differences among individuals with overweight or obesity may result in varied responses to taurine supplementation. This study aims to estimate the effects of long-term taurine supplementation on blood lipids, glycemia, and insulin sensitivity in adults with overweight or obesity through a systematic review and meta-analysis. Methods: The literature search was based on six databases (Web of Science, PubMed, Scopus, EMBASE, Cochrane, and SPORTDiscus) up to October 2024. Subgroup analyses were performed based on daily taurine intake dosage (<3 g or 3 g), overweight (BMI 25–29.9 kg/m²), and obesity (BMI ≥30 kg/m²). Results: The final number of studies that met the inclusion criteria was 9 RCTs. The overall analysis showed that taurine supplementation significantly decreased TG (WMD = −0.56 mg/dL, 95% CI: −0.92 to −0.2, p = 0.002, I² = 63%), TC (WMD = −0.71 mg/dL, 95% CI: −1.17 to −0.25, p = 0.002, I² = 73%), and fasting insulin (WMD = −2.15 µU/mL, 95% CI: −3.24 to −1.06, p = 0.0001, I² = 9%). In the subgroup analysis, long-term taurine intake led to BMI improvement in overweight adults (WMD = −1.14 kg/m², 95% CI: −1.81 to −0.47, p = 0.0008, I² = 0%). Meanwhile, improvements in HbA1c (WMD = −0.33%, 95% CI: −0.53 to −0.12, p = 0.002, I² = 16%) and HOMA-IR (WMD = −0.91, 95% CI: −1.74 to −0.08, p = 0.003, I² = 54%) were observed only in obese participants following taurine supplementation. Additionally, the long-term intake of 3 g of taurine significantly improved HbA1c (WMD = −0.37%, 95% CI: −0.61 to −0.13, p = 0.003, I² = 0%) and FPG levels (WMD = −7.14 mg/dL, 95% CI: −12.53 to −1.74, p = 0.003, I² = 70%) in overweight/obesity. Conclusions: Long-term taurine supplementation is particularly effective in improving glycemic control and insulin sensitivity in obesity. Furthermore, higher doses of taurine (3 g per day) demonstrate even greater improvements in glycemic control.

The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.

Metabolic diseases, characterized by dysregulated energy homeostasis, represent a major global health challenge. While research has traditionally focused on glucose and lipid metabolism, emerging metabolomic and epidemiological evidence implicates circulating amino acid imbalances as a key factor for metabolic diseases. Phenylalanine (Phe) is an essential aromatic amino acid primarily metabolized by hepatic phenylalanine hydroxylase. Epidemiological investigation demonstrates that elevated plasma Phe is a significant risk factor for obesity, type 2 diabetes mellitus (T2DM) and cancer. Mechanistically, phenylalanyl-tRNA synthetase mediates phenylalanylation of insulin receptor β, subsequently inhibiting insulin signal transduction. Meanwhile, Phe and its catabolites (e.g., phenylpyruvate) impair mitochondrial function, induce oxidative stress, and inflammation, ultimately lead to insulin resistance and hepatic steatosis. Interestingly, the derivatives of Phe(such as exercise-induced N-lactoylphenylalanine) can suppress appetite and improve glucose homeostasis, suggesting functional diversity in the Phe metabolic network. In addition, clinical therapeutic strategies are gradually transitioning from traditional strict dietary restriction to personalized and multimodal interventions including nutrition, pharmacology and enzyme replacement therapy. However, ensuring the continuity, efficacy and safety of the treatment strategy remains a formidable challenge. In conclusion, this review explores the pathophysiological impact of Phe by integrating the epidemiological and molecular evidence for its role in metabolic diseases. From a translational medicine perspective, we further evaluate current therapeutic strategies, aiming to promote the clinical translation of Phe metabolism.