Predictive Efficiency of Prediabetes for Diabetes Among Chinese Middle-Aged and Older Populations: a 5-Year National Prospective Cohort Study.

BACKGROUND: Limited studies have explored the predictive efficiency of prediabetes based on two definitions for diabetes among Chinese middle-aged and older populations with prediabetes. OBJECTIVE: To evaluate the predictive efficiency of prediabetes based on two definitions for diabetes and the clinical and public health benefit in Chinese middle-aged and older populations. DESIGN: A 5-year cohort study from the China Health and Retirement Longitudinal Study. PARTICIPANTS: A total of 5208 participants who had blood sample data at baseline in 2011. MAIN MEASURES: The exposure was prediabetes based on American Diabetes Association (ADA) and World Health Organization (WHO) definition. The main outcome was incident diabetes. The ability of prediabetes for predicting diabetes was assessed by sensitivity, specificity, positive predictive value, and negative predictive value. Cox proportional hazards regression was used to explore the associations between prediabetes and the 5-year risk of diabetes and all-cause mortality. KEY RESULTS: Among those with prediabetes according to the ADA definition, only 426 (15.45%) with baseline prediabetes progressed to total diabetes, while according to the WHO definition, 208 (21.89%) progressed to total diabetes. In terms of the ability of predicting the incident total diabetes in 5 years, the ADA definition has a higher sensitivity than the WHO definition (70.76% versus 34.55%, P < 0.001), while the WHO definition has a higher specificity than the ADA definition (84.09% versus 49.35%, P < 0.001). Positive predictive values based on the two definitions were low (< 24%); negative predictive values were high (> 90%). CONCLUSIONS: Neither definition of prediabetes is robust for predicting diabetes development in Chineses middle-aged and older populations.

Upper arm length and knee height are associated with diabetes in the middle-aged and elderly: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVE: To determine if limb lengths, as markers of early life environment, are associated with the risk of diabetes in China. DESIGN: We performed a cohort analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), and multivariable-adjusted Cox proportional hazard regression models were used to examine the associations between baseline limb lengths and subsequent risk of diabetes. SETTING: The CHARLS, 2011-2018. PARTICIPANTS: The study confined the eligible subject to 10 711 adults aged over 45 years from the CHARLS. RESULTS: During a mean follow-up period of 6·13 years, 1358 cases of incident diabetes were detected. When controlling for potential covariates, upper arm length was inversely related to diabetes (hazard ratio (HR) 0·95, 95 % CI (0·91, 0·99), P = 0·028), and for every 1-cm difference in knee height, the risk of diabetes decreased by about 4 % (HR 0·96, 95 % CI (0·93, 0·99), P = 0·023). The association between upper arm length and diabetes was only significant among females while the association between knee height and diabetes was only significant among males. In analyses stratified by BMI, significant associations between upper arm length/knee height and diabetes only existed among those who were underweight (HR 0·91, 95 % CI (0·83, 1·00), P = 0·049, HR 0·92, 95 % CI (0·86, 0·99), P = 0·031). CONCLUSIONS: Inverse associations were observed between upper arm length, knee height and the risk for diabetes development in a large Asian population, suggesting early life environment, especially infant nutritional status, may play an important role in the determination of future diabetes risk.

Obesity and risk of hearing loss in the middle-aged and elderly: a national cohort of Chinese adults.

BACKGROUND: The relationship between obesity and hearing loss among the middle-aged and older population remained unclear. Moreover, few studies have focused on the impact of gender on this association. METHODS: This cohort study extracted the data from the China Health and Retirement Longitudinal Study, a national survey of adults aged 45 years or over. Waist circumference was categorized into three groups: normal, pre-central obesity, and central obesity. We classified BMI into four categories: underweight, normal weight, overweight, and obese. The primary endpoint was the incidence of self-reported hearing loss. RESULTS: Of the 14,237 participants, 1972 incidents of hearing loss were identified during a median 6.9 years of follow-up. The cumulative incidence of hearing loss was 13.9% (95% CI 13.3% -14.4%). Our study showed that central obesity was significantly associated with hearing loss (HR 0.84, 95%CI 0.75-0.94), and this relationship was more prominent in males (HR 0.76, 95%CI 0.63-0.91). Among male participants, the underweight group was at the highest risk of hearing loss (HR 1.39, 95%CI 1.08-1.79). Compared with the normal weight group, the adjusted HR for hearing loss in the obese groups was 0.69 (95%CI 0.51-0.94) among men. Among female participants, only the overweight group had a lower risk of hearing loss than the normal weight group (HR 0.83, 95%CI 0.71-0.96). CONCLUSIONS: Being overweight and obese were significantly associated with a decreased risk of hearing loss, whereas being underweight was associated with an increased risk of hearing loss.

Theoretical and numerical modeling of Rayleigh wave scattering by an elastic inclusion.

This work presents theoretical and numerical models for the backscattering of two-dimensional Rayleigh waves by an elastic inclusion, with the host material being isotropic and the inclusion having an arbitrary shape and crystallographic symmetry. The theoretical model is developed based on the reciprocity theorem using the far-field Green's function and the Born approximation, assuming a small acoustic impedance difference between the host and inclusion materials. The numerical finite element (FE) model is established to deliver a relatively accurate simulation of the scattering problem and to evaluate the approximations of the theoretical model. Quantitative agreement is observed between the theoretical model and the FE results for arbitrarily shaped surface/subsurface inclusions with isotropic/anisotropic properties. The agreement is excellent when the wavelength of the Rayleigh wave is larger than, or comparable to, the size of the inclusion, but it deteriorates as the wavelength gets smaller. Also, the agreement decreases with the anisotropy index for inclusions of anisotropic symmetry. The results lay the foundation for using Rayleigh waves for quantitative characterization of surface/subsurface inclusions, while also demonstrating its limitations.

The Transcription Factor ZmNAC89 Gene Is Involved in Salt Tolerance in Maize (Zea mays L.).

The NAC gene family has transcription factors specific to plants, which are involved in development and stress response and adaptation. In this study, ZmNAC89, an NAC gene in maize that plays a role in saline-alkaline tolerance, was isolated and characterized. ZmNAC89 was localized in the nucleus and had transcriptional activation activity during in vitro experiments. The expression of ZmNAC89 was strongly upregulated under saline-alkaline, drought and ABA treatments. Overexpression of the ZmNAC89 gene in transgenic Arabidopsis and maize enhanced salt tolerance at the seedling stage. Differentially expressed genes (DEGs) were then confirmed via RNA-sequencing analysis with the transgenic maize line. GO analyses showed that oxidation-reduction process-regulated genes were involved in ZmNAC89-mediated salt-alkaline stress. ZmNAC89 may regulate maize saline-alkali tolerance through the REDOX pathway and ABA signal transduction pathway. From 140 inbred maize lines, 20 haplotypes and 16 SNPs were found in the coding region of the ZmNAC89 gene, including the excellent haplotype HAP20. These results contribute to a better understanding of the response mechanism of maize to salt-alkali stress and marker-assisted selection during maize breeding.

MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis.

Cholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1-/--BDL mice showed mitigation of cholestatic liver injury. On a molecular level, the pro-proliferative IL-6/AKT feedback loop was activated in Mir200c-/- livers but was inhibited in Sesn1-/- livers upon cholestasis in mice. Furthermore, rescuing expression of miR-200c by the adeno-associated virus serotype 8 ameliorated BDL-induced liver injury in Mir200c-/- mice. Taken together, this study demonstrates that miR-200c restrains the proliferative and neuroendocrine-like activation of cholangiocytes by targeting SESN1 and inhibiting the IL-6/AKT feedback loop to protect against cholestatic liver fibrosis. Our findings provide mechanistic insights regarding biliary liver fibrosis, which may help to reveal novel therapeutic targets for the treatment of cholestatic liver injury and liver fibrosis.

Liver cyclophilin D deficiency inhibits the progression of early NASH by ameliorating steatosis and inflammation.

Cyclophilin D (CypD) can stimulate the opening of the membrane permeability transition pore (mPTP) and regulate mitochondrial function. Whole-body knockout of CypD improved high fat diet-induced hepatic steatosis by reducing the excess opening of the mPTP and lipid deposition. However, whether CypD significantly ameliorates nonalcoholic steatohepatitis (NASH) has not been studied. Therefore, we established liver-specific CypD knockout (CypD LKO) mice and fed a HFHC diet to induce NASH. Compared with the wild-type mice, the CypD LKO not only showed improved lipid deposition and insulin resistance by increasing fatty acid oxidation but also displayed ameliorated hepatic inflammation, although the symptoms of fibrosis in the NASH model were not significantly improved. In addition, we used bile duct ligation (BDL) or a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to induce cholestatic disease and found that CypD LKO had also no significant effect on acute fibrosis. Thus, CypD LKO can inhibit the progression of early NASH by ameliorating steatosis and inflammatory symptoms. These results suggest a new strategy for the treatment of early NASH.

Sex-Specific Associations Between Diabetes Mellitus and Hearing Loss in the Middle-Aged and Elderly Individuals: A National Cohort Study of Chinese Adults.

OBJECTIVE: To examine the association between diabetes and hearing loss and whether the association varied by sex. METHODS: This cohort study based on nationally representative data from the China Health and Retirement Longitudinal Study included 16 140 Chinese adults aged >45 years between 2011 and 2018. Diabetes was identified by blood glucose levels, HbA1c levels, and a self-reported diagnosis at baseline. The main outcome was self-reported incident hearing loss. Cox proportional hazards regression models were performed to estimate the risk of hearing loss. RESULTS: We documented 2388 cases of hearing loss during a median 6.9 years of follow-up. The incidence rates were 29.64 (95% CI, 28.07-31.29) per 1000 person-years in women and 25.23 (95% CI, 23.77-26.78) per 1000 person-years in men. After adjustment, the hazard ratios of hearing loss associated with diabetes were 1.20 (95% CI, 1.01-1.42) for women and 0.97 (95% CI, 0.78-1.19) for men. Compared with poor control of the blood sugar levels, the odds ratio for hearing loss for women with good glycemic control was reduced from 5.08 (95% CI, 1.31-19.66) to 1.26 (95% CI, 0.69-2.28), and the corresponding odds ratio for men was 1.65 (95% CI, 0.61-4.44) to 0.50 (95% CI, 0.18-1.38). CONCLUSION: In conclusion, we identified a differential effect of sex on hearing loss risk with more pronounced effects for women. Our data suggest that good blood glucose level control is helpful to prevent hearing loss.

Evaluating elongated grains with diffuse ultrasonic double scattering and rectangular transducers.

Diffuse scattering of ultrasound by the microstructure of polycrystal specimens can be used to evaluate grain size and grain elongation. The existing diffuse scattering models mostly dealt with circular transducers whose symmetrical sound field is insensitive to the asymmetric elongated grain. The sound field of a rectangular transducer provides a new perspective for acquiring additional information. First, the existing single scattering response (SSR) and double scattering response (DSR) models are modified for a rectangular transducer, where the sound field of a rectangular transducer is equivalent to that of an elliptical transducer in the far-field. Therefore, an equivalent single Gaussian beam model is derived using amplitude-equivalent and beamwidth-equivalent coefficients. Then, the spatial correlation function of elongated grains is transformed into the wavenumber domain, giving rise to the SSR and DSR of a rectangular transducer that reveals the interaction effect of an asymmetric sound field and elongated grains on ultrasonic backscattering. The experimental results show that the sizes of elongated grains in a cold-rolled aluminum are evaluated as 1086 ± 8, 90 ± 4, and 10 ± 1 µm in the x, y, and z directions, where the exact values are 1184.2 ± 11.9, 80.7 ± 5.2, and 8.3 ± 0.5 µm according to metallographic measurements.

Attenuation and dispersion of leaky Rayleigh wave in polycrystals.

In this work, we use the characteristic equation of leaky Rayleigh waves (LRWs) and a unified approach of bulk waves proposed by Stanke and Kino [J. Acoust. Soc. Am. 75, 665-681 (1984)] to calculate the attenuation and velocity dispersion of LRWs in polycrystals. Numerical results demonstrate that the total attenuation including the leakage attenuation and scattering attenuation is proportional to frequency and independent of grain size in the Rayleigh scattering regime. Meanwhile, the variation of phase velocity in all scattering regimes remains at ∼0.7% according to the theoretical expectation; this means that the velocity dispersion of the LRWs can be ignored, consistent with the conventional viewpoint. Measurements are conducted on stainless steel at different ultrasonic frequencies (all in the Rayleigh scattering regime). The non-paraxial sound field model is used here to eliminate the diffraction loss and to obtain the total attenuation. Experimental results verify that LRWs have very little velocity dispersion. Meanwhile, experimental fitting data reveal that the modified theoretical model can be used to evaluate the total attenuation (only ∼2% discrepancies) of LRWs under the consideration of the diffraction effect. The relative errors between experimental scattering attenuation and theoretical value ranged from 11% to 18%, mainly owing to the effect of surface roughness and measurement inaccuracy.

Identification of miRNAs Mediating Seed Storability of Maize during Germination Stage by High-Throughput Sequencing, Transcriptome and Degradome Sequencing.

Seed storability is an important trait for improving grain quality and germplasm conservation, but little is known about the regulatory mechanisms and gene networks involved. MicroRNAs (miRNAs) are small non-coding RNAs regulating the translation and accumulation of their target mRNAs by means of sequence complementarity and have recently emerged as critical regulators of seed germination. Here, we used the germinating embryos of two maize inbred lines with significant differences in seed storability to identify the miRNAs and target genes involved. We identified a total of 218 previously known and 448 novel miRNAs by miRNA sequencing and degradome analysis, of which 27 known and 11 newly predicted miRNAs are differentially expressed in two maize inbred lines, as measured by Gene Ontology (GO) enrichment analysis. We then combined transcriptome sequencing and real-time quantitative polymerase chain reaction (RT-PCR) to screen and confirm six pairs of differentially expressed miRNAs associated with seed storability, along with their negative regulatory target genes. The enrichment analysis suggested that the miRNAs/target gene mediation of seed storability occurs via the ethylene activation signaling pathway, hormone synthesis and signal transduction, as well as plant organ morphogenesis. Our results should help elucidate the mechanisms through which miRNAs are involved in seed storability in maize.

Propagation of leaky Rayleigh waves along a curved fluid-solid interface.

A characteristic equation is derived for a leaky Rayleigh wave (LRW), propagating on a curved fluid-solid interface. The equations of motion for the curved solid and fluid are formulated using the constitutive equations of a homogenous isotropic curved solid and an inviscid fluid, respectively. The displacement potential functions are used to simplify the derivation. The interface conditions are used to ensure continuities of the mass, momentum, and energy across the interface. Then, with the consideration of the interface radius of the curvature, the characteristic equation for the LRW is established and solved numerically by Muller's method. One important outcome is that there is weaker directional dependence for the velocity of the LRWs on the radius of curvature in comparison with the Rayleigh waves at an air-solid interface. However, the numerical results show a strong directional dependence for the attenuation due to the LRW leakage on the complex curvatures. Moreover, a quantitative relation between the curvature and attenuation caused by the leakage for different materials is shown. The results are significant especially with respect to relevant future applications of ultrasonic testing.

Solid fuel use for heating and risks of breast and cervical cancer mortality in China.

BACKGROUND: Carcinogens released from indoor burning of solid fuels are believed to enter the bloodstream and to be metabolized in breast and cervical tissues. Little evidence exists about the relationship of solid fuel use from heating with breast and cervical cancer. OBJECTIVES: To examine the association of solid heating fuel use with breast and cervical cancer mortality. METHODS: This study included female participants aged 30-79 years who were enrolled in the China Kadoorie Biobank during 2004-2008 from 10 diverse regions across China. During a 10.2-year median follow-up, 177 breast cancer deaths and 113 cervical cancer deaths were documented. Multivariable Cox regression models yielded adjusted hazard ratios (HRs) for the associations of self-reported long-term heating fuel exposure with two cancer deaths. Stratified analyses were used to assess effect modification. RESULTS: We included 236,116 participants for breast cancer analyses and 228,795 for cervical cancer analyses. Compared with non-solid fuel use, the fully adjusted HRs of cervical cancer deaths were 1.75 (0.91-3.38) for wood use, 2.23 (1.09-4.59) for mixed fuel (coal and wood) use. No evident relationship was observed for breast cancer deaths. Cervical cancer risk increased with the duration of solid fuel use (P for trend = 0.041). Elevated cervical cancer risk was observed in post-menopausal women (HR 2.01, 1.01-4.03), not in pre-menopausal women (HR 0.77, 0.56-2.31) (P for heterogeneity = 0.004); and in those aged ≥50 years (HR 2.56, 1.17-5.86), not in those aged < 50 years (HR 0.69, 0.26-1.84) (P < 0.001). CONCLUSION: Indoor solid fuel combustion for heating may be associated with a higher risk for cervical cancer death, but not for breast cancer. The strength of the association increased with the duration of exposure and was modified by age and menopause status.

Higher-order spatial correlation coefficients of ultrasonic backscattering signals using partial cross-correlation analysis.

The spatial correlation properties of ultrasonic backscattering signals in random media have important implications. For example, they can be used for microstructural characterization and flaw detection in engineering materials. However, the traditional spatial correlation coefficient (SCC) is only a leading order quantity that does not capture the true spatial correlations of random media. This is caused by neglecting confounding variables such as non-zero means or other non-zero odd-order moments. Here, the SCC is generalized from zeroth- to general-order through partial cross-correlation analysis. A series of indicators are defined to quantify the SCC curve at zero time lag, and the maximum time shift curve, which are both functions of lateral separation between two sensor positions. A stainless-steel specimen and a focused ultrasonic transducer are used to verify the method. Scattering measurements show that the higher-order SCC can consistently capture spatial correlations whereas the zeroth-order SCC is inadequate. The zeroth-order SCC is shown to predict a step size that can be more than six times too large. Thus, the present method can provide better understanding of statistical correlations and conditions to measure uncorrelated backscattering signals.

ER stress contributes to high-fat diet-induced decrease of thyroglobulin and hypothyroidism.

Recent studies revealed the emerging role of excess uptake of lipids in the development of hypothyroidism. However, the underlying mechanism is largely unknown. We investigated the effect of high-fat diet (HFD) on thyroid function and the role of endoplasmic reticulum (ER) in HFD-induced hypothyroidism. Male Sprague-Dawley rats were fed with HFD or control diet for 18 wk. HFD rats showed an impaired thyroid function, with decreased thyroglobulin (Tg) level. We found the ER stress was triggered in HFD rat thyroid glands and palmitate-treated thyrocytes. Luminal swelling of ER in thyroid epithelial cells of HFD rats was also observed. The rate of Tg degradation increased in palmitate-treated thyrocytes. In addition, applying 4-phenyl butyric acid to alleviate ER stress in HFD rats improved the decrease of Tg and thyroid function. Withdrawal of the HFD improved thyroid function . In conclusion, we demonstrate that ER stress mediates the HFD-induced hypothyroidism, probably by impairing the production of Tg, and attenuation of ER stress improves thyroid function. Our study provides the understanding of how HFD induces hypothyroidism.

Cyclophilin D deficiency attenuates mitochondrial perturbation and ameliorates hepatic steatosis.

Physiological opening of the mitochondrial permeability transition pore (mPTP) is indispensable for maintaining mitochondrial function and cell homeostasis, but the role of the mPTP and its initial factor, cyclophilin D (CypD), in hepatic steatosis is unclear. Here, we demonstrate that excess mPTP opening is mediated by an increase of CypD expression induced hepatic mitochondrial dysfunction. Notably, such mitochondrial perturbation occurred before detectable triglyceride accumulation in the liver of high-fat diet-fed mice. Moreover, either genetic knockout or pharmacological inhibition of CypD could ameliorate mitochondrial dysfunction, including excess mPTP opening and stress, and down-regulate the transcription of sterol regulatory element-binding protein-1c, a key factor of lipogenesis. In contrast, the hepatic steatosis in adenoviral overexpression of CypD-infected mice was aggravated relative to the control group. Blocking p38 mitogen-activated protein kinase or liver-specific Ire1α knockout could resist CypD-induced sterol regulatory element-binding protein-1c expression and steatosis. Importantly, CypD inhibitor applied prior to or after the onset of triglyceride deposition substantially prevented or ameliorated fatty liver. CONCLUSION: CypD stimulates mPTP excessive opening, subsequently causing endoplasmic reticulum stress through p38 mitogen-activated protein kinase activation, and results in enhanced sterol regulatory element-binding protein-1c transcription and hepatic steatosis. (Hepatology 2018;68:62-77).

Flaw detection with ultrasonic backscatter signal envelopes.

Ultrasound is a prominent nondestructive testing modality for the detection, localization, and sizing of defects in engineering materials. Often, inspectors analyze ultrasonic waveforms to determine if echoes, which stem from the scattering of ultrasound from a defect, exceed a threshold value. In turn, the initial selection of the threshold value is critical. In this letter, a time-dependent threshold or upper bound for the signal envelope is developed based on the statistics governing the scattering of ultrasound from microstructure. The utility of the time-dependent threshold is demonstrated using experiments conducted on sub-wavelength artificial defects. The results are shown to enhance current nondestructive inspection practices.

Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice.

AIMS/HYPOTHESIS: Increased serum follicle-stimulating hormone (FSH) is correlated with fasting hyperglycaemia. However, the underlying mechanism remains unclear. Because excessive hepatic gluconeogenesis is a major cause of fasting hyperglycaemia the present study investigated whether FSH increases hepatic gluconeogenesis in mice. METHODS: Ovariectomised mice supplemented with oestradiol (E2) to maintain normal levels of serum E2 (OVX+E2 mice) were injected with low or high doses of FSH. We knocked out Crtc2, a crucial factor in gluconeogenesis, and Fshr to discern their involvement in FSH signalling. To evaluate the role of the G-protein-coupled receptor (GPCR) kinase 2 (GRK2), which could affect glucose metabolism and interact directly with non-GPCR components, a specific GRK2 inhibitor was used. The pyruvate tolerance test (PTT), quantification of PEPCK and glucose-6-phosphatase (G6Pase), key enzymes of gluconeogenesis, GRK2 and phosphorylation of AMP-activated protein kinase (AMPK) were examined to evaluate the level of gluconeogenesis in the liver. A nonphosphorylatable mutant of AMPK Ser485 (AMPK S485A) was transfected into HepG2 cells to evaluate the role of AMPK Ser485 phosphorylation. RESULTS: FSH increased fasting glucose (OVX+E2+high-dose FSH 8.18 ± 0.60 mmol/l vs OVX+E2 6.23 ± 1.33 mmol/l), the PTT results, and the transcription of Pepck (also known as Pck1; 2.0-fold increase) and G6pase (also known as G6pc; 2.5-fold increase) in OVX+E2 mice. FSH also enhanced the promoter luciferase activities of the two enzymes in HepG2 cells. FSH promoted the membrane translocation of GRK2, which is associated with increased AMPK Ser485 and decreased AMPK Thr172 phosphorylation, and enhanced the nuclear translocation of cyclic AMP-regulated transcriptional coactivator 2 (CRTC2). GRK2 could bind with AMPK and induce Ser485 hyperphosphorylation. Furthermore, either the GRK2 inhibitor or AMPK S485A blocked FSH-regulated AMPK Thr172 dephosphorylation and gluconeogenesis. Additionally, the deletion of Crtc2 or Fshr abolished the function of FSH in OVX+E2 mice. CONCLUSIONS/INTERPRETATION: The results indicate that FSH enhances CRTC2-mediated gluconeogenesis dependent on AMPK Ser485 phosphorylation via GRK2 in the liver, suggesting an essential role of FSH in the pathogenesis of fasting hyperglycaemia.

Ablation of prolactin receptor increases hepatic triglyceride accumulation.

Increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide has necessitated a more thorough understanding of it and expanded the scope of research in this field. Women are more resistant to NAFLD than men despite equal exposure to major risk factors, such as obesity or hyperlipidemia. Female resistance is hormone-dependent, as evidenced by the sharp increase in NAFLD incidence in post-menopausal women who do not take hormone replacement therapy. Here, we found that the estrogen-responsive pituitary hormone prolactin (PRL), through specific PRL receptor (PRLR), down-regulates hepatic triglyceride (TG) accumulation. PRL was demonstrated to significantly down-regulate hepatic TG accumulation in female mice and protect male mice from liver steatosis induced by high-fat diet. Interestingly, Ad-shPRLR injected mice, whose hepatic PRLR abundance was effectively decreased at the protein levels, exhibited significantly aggravated liver steatosis. PRL could decrease the expression of stearoyl-coenzyme A desaturase 1 (SCD1), the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, in animal models and multiple hepatic cell lines. Following knockdown of PRLR, the changes to PRL-triggered SCD1 expression disappeared. Thus, PRL acted as a previously unrecognized master regulator of liver TG metabolism, indicating that modification of PRL via PRLR might serve as a potential therapeutic target for NAFLD.