High fat diet rescues disturbances to metabolic homeostasis and survival in the Id2 null mouse in a sex-specific manner

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have altered expression of circadian genes involved in lipid metabolism, altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue. Here we further characterized the Id2−/− mouse metabolic phenotype in a sex-specific context and under low and high fat diets, and examined metabolic and endocrine parameters associated with lipid and glucose metabolism. Under the low-fat diet Id2−/− mice showed decreased weight gain, reduced gonadal fat mass, and a lower survival rate. Under the high-fat diet, body weight and gonadal fat gain of Id2−/− male mice was comparable to control mice and survival rate improved markedly. Furthermore, the high-fat diet treated Id2−/− male mice lost the enhanced glucose tolerance feature observed in the other Id2−/− groups, and there was a sex-specific difference in white adipose tissue storage of Id2−/− mice. Additionally, a distinct pattern of hepatic lipid accumulation was observed in Id2−/− males: low lipids on the low-fat diet and steatosis on the high-fat diet. In summary, these data provides valuable insights into the impact of Id2 deficiency on metabolic homeostasis of mice in a sex-specific manner

More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measurements, were mostly restricted to data from single countries. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change+/-100) revealed a mean reduction of smell (-79.7+/- 28.7, mean+/- SD), taste (-69.0+/- 32.6), and chemesthetic (-37.3+/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.Additional co-authors: Veronica Pereda-Loth, Shannon B Olsson, Richard C Gerkin, Paloma Rohlfs Domínguez, Javier Albayay, Michael C. Farruggia, Surabhi Bhutani, Alexander W Fjaeldstad, Ritesh Kumar, Anna Menini, Moustafa Bensafi, Mari Sandell, Iordanis Konstantinidis, Antonella Di Pizio, Federica Genovese, Lina Öztürk, Thierry Thomas-Danguin, Johannes Frasnelli, Sanne Boesveldt, Özlem Saatci, Luis R. Saraiva, Cailu Lin, Jérôme Golebiowski, Liang-Dar Hwang, Mehmet Hakan Ozdener, Maria Dolors Guàrdia, Christophe Laudamiel, Marina Ritchie, Jan Havlícek, Denis Pierron, Eugeni Roura, Marta Navarro, Alissa A. Nolden, Juyun Lim, KL Whitcroft, Lauren R. Colquitt, Camille Ferdenzi, Evelyn V. Brindha, Aytug Altundag, Alberto Macchi, Alexia Nunez-Parra, Zara M. Patel, Sébastien Fiorucci, Carl M. Philpott, Barry C. Smith, Johan N Lundström, Carla Mucignat, Jane K. Parker, Mirjam van den Brink, Michael Schmuker, Florian Ph.S Fischmeister, Thomas Heinbockel, Vonnie D.C. Shields, Farhoud Faraji, Enrique Enrique Santamaría, William E.A. Fredborg, Gabriella Morini, Jonas K. Olofsson, Maryam Jalessi, Noam Karni, Anna D'Errico, Rafieh Alizadeh, Robert Pellegrino, Pablo Meyer, Caroline Huart, Ben Chen, Graciela M. Soler, Mohammed K. Alwashahi, Olagunju Abdulrahman, Antje Welge-Lüssen, Pamela Dalton, Jessica Freiherr, Carol H. Yan, Jasper H. B. de Groot, Vera V. Voznessenskaya, Hadar Klein, Jingguo Chen, Masako Okamoto, Elizabeth A. Sell, Preet Bano Singh, Julie Walsh-Messinger, Nicholas S. Archer, Sachiko Koyama, Vincent Deary, Hüseyin Yanik, Samet Albayrak, Lenka Martinec Novákov, Ilja Croijmans, Patricia Portillo Mazal, Shima T. Moein, Eitan Margulis, Coralie Mignot, Sajidxa Mariño, Dejan Georgiev, Pavan K. Kaushik, Bettina Malnic, Hong Wang, Shima Seyed-Allaei, Nur Yoluk, Sara Razzaghi, Jeb M. Justice, Diego Restrepo, Julien W Hsieh, Danielle R. Reed, Thomas Hummel, Steven D Munger, John E Haye

Additional file 1 of Perinatal depression and its impact on infant outcomes and maternal-nurse SMS communication in a cohort of Kenyan women

Additional file 1: Supplementary Table A. Baseline Characteristics for Total and Retained Cohorts. Participant baseline characteristics for the 798 participants with complete enrollment data and for the 572 participants with two completed EPDS surveys. Supplementary Table B. Baseline Characteristics of Excluded vs. Retained Cohorts. Comparison of participant baseline characteristics between the 226 participants who were excluded because they did complete a second EPDS survey, and thus did not have a postpartum depression outcome, and the 572 participants included in the study who had two completed EPDS surveys

Ablation of the <i>Id2</i> Gene Results in Altered Circadian Feeding Behavior, and Sex-Specific Enhancement of Insulin Sensitivity and Elevated Glucose Uptake in Skeletal Muscle and Brown Adipose Tissue

<div><p>Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our earlier studies have demonstrated a role for ID2 in the input pathway, core clock function and output pathways of the mouse circadian system. We have also reported that <i>Id2</i> null (<i>Id2</i>−/−) mice are lean with low gonadal white adipose tissue deposits and lower lipid content in the liver. These results coincided with altered or disrupted circadian expression profiles of liver genes including those involved in lipid metabolism. In the present phenotypic study we intended to decipher, on a sex-specific basis, the role of ID2 in glucose metabolism and in the circadian regulation of activity, important components of energy balance. We find that <i>Id2</i>−/− mice exhibited altered daily and circadian rhythms of feeding and locomotor activity; activity profiles extended further into the late night/dark phase of the 24-hr cycle, despite mice showing reduced total locomotor activity. Also, male <i>Id2−/−</i> mice consumed a greater amount of food relative to body mass, and displayed less weight gain. <i>Id2−/−</i> females had smaller adipocytes, suggesting sexual-dimorphic programing of adipogenesis. We observed increased glucose tolerance and insulin sensitivity in male <i>Id2−/−</i> mice, which was exacerbated in older animals. FDG-PET analysis revealed increased glucose uptake by skeletal muscle and brown adipose tissue of male <i>Id2</i>−/− mice, suggesting increased glucose metabolism and thermogenesis in these tissues. Reductions in intramuscular triacylglycerol and diacylglycerol were detected in male <i>Id2</i>−/− mice, highlighting its possible mechanistic role in enhanced insulin sensitivity in these mice. Our findings indicate a role for ID2 as a regulator of glucose and lipid metabolism, and in the circadian control of feeding/locomotor behavior; and contribute to the understanding of the development of obesity and diabetes, particularly in shift work personnel among whom incidence of such metabolic disorders is elevated.</p></div

Skeletal muscle triglyceride (TG) and diacylglycerol (DAG) profiles in <i>Id2−/−</i> mice.

<p>A) Total TG content of tibialis anterior muscle (ANOVA: genotype (G), n.s.; sex (S), P<0.05; interaction (I), n.s.). B) Total DAG content of tibialis anterior muscle (G, n.s.; S, P<0.01; I, n.s.). C) DAG species analysis. DAG species are abbreviated as two contributing fatty acyl groups: A, E, S, O, L and P denote arachidonoyl, eicosapentanoyl, stearoyl, oleoyl, linoleoyl and palmitoyl groups, respectively. Values represent mean ± SEM. *p<0.05, **p<0.01 and ***p<0.001 are Turkey post-hoc tests following two way ANOVA for TG, DAG or each DAG species.</p

Glucose tolerance, insulin sensitivity and insulin release in <i>Id2−/−</i> females is unaltered.

<p>A) GTT of young female <i>Id2−/−</i> and WT mice (RM-ANOVA: time (T), P<0.001; genotype (G), n.s.; interaction (I), n.s.). B) GTT of old female <i>Id2−/−</i> and WT mice (T, P<0.001; G, n.s.; I, n.s.). C) ITT of young female <i>Id2−/−</i> and WT mice (T, P<0.001; genotype, n.s.; I, n.s.). D) ITT of old female <i>Id2−/−</i> and WT mice (T, P<0.001; G, P<0.01; I, n.s.). E) Glucose-stimulated insulin release in young female <i>Id2−/−</i> and WT mice (T, P<0.001; G, n.s.; I, n.s.). F) Glucose-stimulated insulin release in old female <i>Id2−/−</i> and WT mice (T, n.s.; G, P = 0.055; I, n.s.). No effect of aging was observed in the glucose tolerance of either WT or <i>Id2</i>−/− females (RM-ANOVAs, n.s.). An aging effect of insulin sensitivity was observed for WT and <i>Id2</i>−/− females (T, P<0.001; age, P<0.001; I P<0.001). Values shown represent mean ± SEM. **p<0.01.</p

<i>Id2−/−</i> mice exhibit less locomotor activity compared to WT mice.

<p>A) Daily feeding activity counts of <i>Id2−/−</i> and WT mice (ANOVA: genotype, n.s.; sex, n.s.; interaction, n.s). B) Daily general activity counts in <i>Id2−/−</i> and WT mice determined by passive infrared motion detectors (genotype, P<0.05; sex, P = 0.057; interaction, n.s). C) Daily wheel revolution counts of WT and <i>Id2−/−</i> mice (genotype, P<0.001; sex, P<0.05; interaction, P<0.01). Values represent mean ± SEM. ***p<0.001.</p

Cell size of the gonadal white adipose tissue is different between female <i>Id2−/−</i> and WT mice.

<p>A) Representative images of hematoxylin/eosin stained gonadal white adipose tissue sections of male and female WT and <i>Id2−/−</i> mice (scale bar = 50 µm). B) Cell area of gonadal WAT in WT and <i>Id2−/−</i> mice (ANOVA: genotype, P<0.05; sex, n.s.; interaction, P<0.001). No significant correlation was detected between cell size and age of animal (Spearman’s rank order correlation/linear regression, n.s.).</p

<i>Id2−/−</i> mice show altered daily and circadian patterns of feeding and locomotor activity.

<p>A) Daily feeding activity profile of WT and <i>Id2−/−</i> mice (ANOVA: time (T), P<0.001; genotype (G), n.s.; interaction (I), P<0.01). B) Circadian feeding activity profile of WT and <i>Id2−/−</i> mice (T, P<0.001; G, n.s.; I, P<0.05). C) Daily PIR motion detector general activity profile of WT and <i>Id2−/−</i> mice (T, P<0.001; G, P<0.05; I, P<0.001). D) Circadian general activity profile of WT and <i>Id2−/−</i> mice (T, P<0.001; G, P = 0.15; I, P<0.001). E) Daily wheel running activity profile of WT and <i>Id2−/−</i> mice (T, P<0.001; G, P<0.001; I, P<0.001). F) Circadian wheel running activity profile of WT and <i>Id2−/−</i> mice (T, P<0.001; G, P<0.01; I, P<0.001). The shaded area in the plots represents dark phase of the LD cycle or constant darkness. Values shown represent mean ± SEM. *p<0.05, **p<0.01 and ***p<0.001.</p

Fasting glucose and Insulin levels while aging.

<p>A) Fasting blood glucose levels of young and old, WT and <i>Id2−/−</i> mice (ANOVA: genotype, P<0.01; age, P<0.001; interaction, n.s.). B). Fasting insulin levels of young and old, WT and <i>Id2−/−</i> mice (genotype, P<0.001; age, P<0.05; interaction, n.s.). Values shown represent mean ± SEM. *p<0.05, **p<0.01 and ***p<0.001.</p