A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota–host cross-talk. We developed an enzyme activity–screening platform to investigate how gut microbiota–derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.

Context Homocysteine (Hcy), a known risk factor for cardiovascular disease, has been reported to be linked with thyroid dysfunction. However, the association of thyroid hormones sensitivity with Hcy levels remains unknown. Objective We aimed to investigate the relationship between thyroid hormone sensitivity and elevated Hcy levels in the euthyroid population. Methods A total of 8957 euthyroid adults were included in this study. Free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), Hcy levels, and other clinical parameters were measured. Hyperhomocysteinemia (HHcy) was defined as serum Hcy level > 15 μmol/L. Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), Chinese-referenced parametric TFQI (PTFQI), TSH index (TSHI) and thyrotropin thyroxine resistance index (TT4RI). Results Subjects with decreased sensitivity to thyroid hormones had higher Hcy levels (P for trend < 0.001). Logistic regression analysis revealed the higher quartiles of TFQI, PTFQI, TSHI, and TT4RI were significantly associated with elevated Hcy levels, and these associations remained significant even after adjustment for multiple risk factors. After adjusting for age, sex, body mass index, dyslipidemia, fatty liver, diabetes, and hypertension, the odds ratio (95% CI) for having HHcy of the TFQI in the highest quartile was 1.393 (1.210, 1.603), the PTFQI in the highest quartile was 1.409 (1.225, 1.621), the TSHI in the highest quartile was 1.372 (1.190, 1.583), and the TT4RI in the highest quartile was 1.315 (1.141, 1.515) (all P < 0.001). Conclusion In euthyroid subjects, impaired sensitivity to thyroid hormones was associated with elevated Hcy levels.

Background: Meteorin-like (Metrnl), a novel adipokine, is highly expressed in adipose tissue and has a beneficial effect on energy metabolism. However, data on circulating Metrnl levels in obesity are scarce and inconsistent. This study aimed to evaluate the serum levels of Metrnl in adults with obesity and its association with glucose and lipid metabolism.Methods: 182 subjects were included in the cross-sectional study. The participants were divided into three groups according to BMI: normal (n = 95), overweight (n = 46), and obesity (n = 41). Serum Metrnl concentrations were measured by enzyme-linked immunosorbent assay.Results: Serum Metrnl levels in overweight or obese subjects were significantly lower than in the normal group. Circulating Metrnl levels were negatively correlated with TG, TC, LDL-C, and sdLDL and positively correlated with HDL-C before and after adjusting for age, sex, BMI, diabetes, HOMA-IR, and eGFR (all P < 0.05). Furthermore, logistic regression analysis indicated that compared with the highest tertile, the lowest tertile of Metrnl levels were significantly associated with the presence of hyper-TG, hyper-TC, and Hyper-LDL after full adjustment (all P for trend < 0.05).Conclusions: Serum Metrnl levels were reduced in individuals with overweight or obesity and were independently associated with adverse lipid profile, suggesting that modifying circulating Metrnl levels may serve as a potential therapeutic target for atherogenic dyslipidemia.

Graves’ disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors. Of these influencing factors, some are modifiable but some are nonmodifiable. The recurrence risk can be reduced by adjusting the modifiable factors as much as possible. The titration regimen for 12–18 months is the optimal strategy of ATD. Levothyroxine administration after successful ATD treatment was not recommended. The addition of immunosuppressive drugs might be helpful to decrease the recurrence rate of GD patients after ATD withdrawal, whereas further studies are needed to address the safety and efficacy. This paper reviewed the current knowledge of ATD treatment and mainly focused on influencing factors for recurrence in GD patients with ATD treatment.

Background: Impaired sensitivity to thyroid hormones (TH) was associated with metabolic syndrome. The study aimed to explore the association between central TH sensitivity indices and insulin resistance (IR) in euthyroid adults with obesity.Methods: This cross-sectional study enrolled 293 euthyroid outpatients with obesity in Beijing Chao-Yang Hospital. We used the thyroid feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotrophic T4 resistance index (TT4RI) to indicate central TH sensitivity. IR was assessed by homeostasis model assessment of insulin resistance (HOMA-IR), hepatic insulin resistance index (hepatic-IR), the Matsuda index, and the adipose tissue insulin resistance index (Adipo-IR). Participants were categorized according to tertiles of TH sensitivity indices. We used multiple linear regressions to explore the associations.Results: There was a significant stepwise increase in HOMA-IR and Adipo-IR from the lowest to the highest tertiles of TH sensitivity indices (all P&lt;0.05). After adjustment for age, sex, body mass index, hypertension, hyperlipidemia, and diabetes, only Adipo-IR was significantly associated with TH sensitivity indices. On average, each unit increased in TFQI, TSHI, and TT4RI was associated with 1.19 (P=0.053), 1.16 (P=0.04), and 1.01 (P=0.03) units increased in Adipo-IR, respectively. There was no significant association between TH sensitivity indices and HOMA-IR, hepatic-IR, and the Matsuda index after adjustment for other risk factors.Conclusions: Reduced central TH sensitivity was associated with increased adipose tissue insulin resistance in euthyroid adults with obesity. The results further confirmed the importance of TH sensitivity on metabolic diseases.