AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

The effects of dietary vitamins, lipids and temperature on teleost immunity

SIGLEAvailable from British Library Document Supply Centre- DSC:DX171129 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Analytical and sampling constraints in ²¹⁰Pb dating

<sup>210</sup>Pb dating provides a valuable, widely used means of establishing recent chronologies for sediments and other accumulating natural deposits. The Constant Rate of Supply (CRS) model is the most versatile and widely used method for establishing <sup>210</sup>Pb chronologies but, when using this model, care must be taken to account for limitations imposed by sampling and analytical factors. In particular, incompatibility of finite values for empirical data, which are constrained by detection limit and core length, with terms in the age calculation, which represent integrations to infinity, can generate erroneously old ages for deeper sections of cores. The bias in calculated ages increases with poorer limit of detection and the magnitude of the disparity increases with age. The origin and magnitude of this effect are considered below, firstly for an idealised, theoretical <sup>210</sup>Pb profile and secondly for a freshwater lake sediment core. A brief consideration is presented of the implications of this potential artefact for sampling and analysis

Mediterranean diet associated with lower frailty risk: A large cohort study of 21,643 women admitted to hospitals

Background Mediterranean diet is traditionally considered as a healthy dietary pattern, while its association with frailty has not been confirmed. This study investigated associations between Mediterranean diet and risk of frailty among women admitted to hospitals in England from an older-aged women’s cohort study. Methods A modified Mediterranean diet was evaluated from a validated 217-item food frequency questionnaire. Incident frailty was determined using a hospital frailty risk score based on linkage to Hospital Episode Statistics up to March 2019. Cox proportional hazard models were conducted to estimate hazard ratios (HR) and 95% confidence intervals (CI). Further subgroup analyses stratified by age and body mass index (BMI), and sensitivity analyses were additionally explored. Results Over a mean follow-up of 13 years, there were 14,838 (68.6%) cases of frailty out of 21,643 individuals included in this study. Compared with low adherence to Mediterranean diet, moderate adherence was associated with 5% (HR = 0.95, 95%CI: 0.91, 0.99) lower risk of frailty, with high adherence associated with even lower risk (HR = 0.89, 95%CI: 0.85, 0.94). The magnitude of above associations remained consistent in subgroups stratified by age and BMI, except the association between moderate adherence and risk of frailty was attenuated in the ≥60-year (HR = 0.99, 95%CI: 0.93, 1.06) and the BMI > 24.9 kg/m2 (HR = 0.97, 95%CI: 0.91, 1.03) subgroups. Conclusions Adherence to Mediterranean diet was associated with lower risk of frailty. The better the adherence, the greater the magnitude of the protective association. Older and overweight women may potentially benefit from greater adherence to the Mediterranean diet regarding frailty prevention

Mediterranean diet associated with lower frailty risk: a large cohort study of 21,643 women admitted to hospitals

Background Mediterranean diet is traditionally considered as a healthy dietary pattern, while its association with frailty has not been confirmed. This study investigated associations between Mediterranean diet and risk of frailty among women admitted to hospitals in England from an older-aged women’s cohort study. Methods A modified Mediterranean diet was evaluated from a validated 217-item food frequency questionnaire. Incident frailty was determined using a hospital frailty risk score based on linkage to Hospital Episode Statistics up to March 2019. Cox proportional hazard models were conducted to estimate hazard ratios (HR) and 95% confidence intervals (CI). Further subgroup analyses stratified by age and body mass index (BMI), and sensitivity analyses were additionally explored. Results Over a mean follow-up of 13 years, there were 14,838 (68.6%) cases of frailty out of 21,643 individuals included in this study. Compared with low adherence to Mediterranean diet, moderate adherence was associated with 5% (HR = 0.95, 95%CI: 0.91, 0.99) lower risk of frailty, with high adherence associated with even lower risk (HR = 0.89, 95%CI: 0.85, 0.94). The magnitude of above associations remained consistent in subgroups stratified by age and BMI, except the association between moderate adherence and risk of frailty was attenuated in the ≥ 60-year (HR = 0.99, 95%CI: 0.93, 1.06) and the BMI > 24.9 kg/m2 (HR = 0.97, 95%CI: 0.91, 1.03) subgroups. Conclusions Adherence to Mediterranean diet was associated with lower risk of frailty. The better the adherence, the greater the magnitude of the protective association. Elderly and overweight women may potentially benefit from greater adherence to the Mediterranean diet regarding frailty prevention