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1. Characterizing the Retinal Phenotype in the High-Fat Diet and Western Diet Mouse Models of Prediabetes

   https://doi.org/10.3390/cells9020464  

   Asare-Bediako, Bright; Noothi, Sunil; Li Calzi, Sergio; Athmanathan, Baskaran; Vieira, Cristiano; Adu-Agyeiwaah, Yvonne; Dupont, Mariana; Jones, Bryce; Wang, Xiaoxin; Chakraborty, Dibyendu; et al (February 2020, Cells)

   null (Ed.)

   We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g, p < 0.0001) as well as a reduced insulin sensitivity index (9.418 vs. 62.01, p = 0.0002) compared to LFD controls. At 6 months, retinal functional testing demonstrated a reduction in a-wave and b-wave amplitudes. At 12 months, mice on HFD showed evidence of increased retinal nerve infarcts and vascular leakage, reduced vascular density, but no increase in number of acellular capillaries compared to LFD mice. In conclusion, the HFD mouse is a useful model for examining the effect of prediabetes and hypercholesterolemia on the retina. The HFD-induced changes appear to occur slower than those observed in type 2 diabetes (T2D) models but are consistent with other retinopathy models, showing neural damage prior to vascular changes. 

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2. Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation

   https://doi.org/10.1002/advs.202206068  

   Wang, Shirong; Zha, Lin; Cui, Xin; Yeh, Yu‐Te; Liu, Ruochuan; Jing, Jia; Shi, Huidong; Chen, Weiping; Hanover, John; Yin, Jun; et al (June 2023, Advanced Science)

   Abstract While extensive investigations have been devoted to the study of genetic pathways related to fatty liver diseases, much less is known about epigenetic mechanisms underlying these disorders. DNA methylation is an epigenetic link between environmental factors (e.g., diets) and complex diseases (e.g., non‐alcoholic fatty liver disease). Here, it is aimed to study the role of DNA methylation in the regulation of hepatic lipid metabolism. A dynamic change in the DNA methylome in the liver of high‐fat diet (HFD)‐fed mice is discovered, including a marked increase in DNA methylation at the promoter of Beta‐klotho (Klb), a co‐receptor for the biological functions of fibroblast growth factor (FGF)15/19 and FGF21. DNA methyltransferases (DNMT) 1 and 3A mediate HFD‐induced methylation at theKlbpromoter. Notably, HFD enhances DNMT1 protein stability via a ubiquitination‐mediated mechanism. Liver‐specific deletion ofDnmt1or3aincreasesKlbexpression and ameliorates HFD‐induced hepatic steatosis. Single‐nucleus RNA sequencing analysis reveals pathways involved in fatty acid oxidation inDnmt1‐deficient hepatocytes. Targeted demethylation at theKlbpromoter increasesKlbexpression and fatty acid oxidation, resulting in decreased hepatic lipid accumulation. Up‐regulation of methyltransferases by HFD may induce hypermethylation of theKlbpromoter and subsequent down‐regulation ofKlbexpression, resulting in the development of hepatic steatosis. 

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3. Germ‐Free C57BL /6 Mice Have Increased Bone Mass and Altered Matrix Properties but Not Decreased Bone Fracture Resistance

   https://doi.org/10.1002/jbmr.4835  

   Vahidi, Ghazal; Moody, Maya; Welhaven, Hope D.; Davidson, Leah; Rezaee, Taraneh; Behzad, Ramina; Karim, Lamya; Roggenbeck, Barbara A.; Walk, Seth T.; Martin, Stephen A.; et al (June 2023, Journal of Bone and Mineral Research)

   ABSTRACT The gut microbiome impacts bone mass, which implies a disruption to bone homeostasis. However, it is not yet clear how the gut microbiome affects the regulation of bone mass and bone quality. We hypothesized that germ‐free (GF) mice have increased bone mass and decreased bone toughness compared with conventionally housed mice. We tested this hypothesis using adult (20‐ to 21‐week‐old) C57BL/6J GF and conventionally raised female and male mice (n = 6–10/group). Trabecular microarchitecture and cortical geometry were measured from micro–CT of the femur distal metaphysis and cortical midshaft. Whole‐femur strength and estimated material properties were measured using three‐point bending and notched fracture toughness. Bone matrix properties were measured for the cortical femur by quantitative back‐scattered electron imaging and nanoindentation, and, for the humerus, by Raman spectroscopy and fluorescent advanced glycation end product (fAGE) assay. Shifts in cortical tissue metabolism were measured from the contralateral humerus. GF mice had reduced bone resorption, increased trabecular bone microarchitecture, increased tissue strength and decreased whole‐bone strength that was not explained by differences in bone size, increased tissue mineralization and fAGEs, and altered collagen structure that did not decrease fracture toughness. We observed several sex differences in GF mice, most notably for bone tissue metabolism. Male GF mice had a greater signature of amino acid metabolism, and female GF mice had a greater signature of lipid metabolism, exceeding the metabolic sex differences of the conventional mice. Together, these data demonstrate that the GF state in C57BL/6J mice alters bone mass and matrix properties but does not decrease bone fracture resistance. © 2023 The Authors.Journal of Bone and Mineral Researchpublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). 

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4. Association of male fatty acid intake with fecundability among couples planning pregnancy

   https://doi.org/10.1093/humrep/dead100  

   Geller, Ruth J; Wesselink, Amelia K; Koenig, Martha R; Eisenberg, Michael L; Tucker, Katherine L; Hatch, Elizabeth E; Wise, Lauren A (May 2023, Human Reproduction)

   Abstract STUDY QUESTIONTo what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? SUMMARY ANSWERWe observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability. WHAT IS KNOWN ALREADYMale fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception. STUDY DESIGN, SIZE, DURATIONWe conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015–2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants were residents of the USA or Canada, aged 21–45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation. MAIN RESULTS AND THE ROLE OF CHANCEAmong 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01–1.71), 1.16 (95% CI 0.88–1.51), and 1.43 (95% CI 1.09–1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94–1.55), 1.16 (95% CI 0.89–1.51), and 1.23 (95% CI 0.94–1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner’s intakes of trans- and omega-3 fats. LIMITATIONS, REASONS FOR CAUTIONDietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGSOur results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding. STUDY FUNDING/COMPETING INTEREST(S)The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report. TRIAL REGISTRATION NUMBERN/A. 

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5. Juvenile Dungeness crabs ( Metacarcinus magister ) selectively integrate and modify the fatty acids of their experimental diets

   https://doi.org/10.1098/rstb.2020.0038  

   Thomas, Michael D.; Schram, Julie B.; Clark-Henry, Zade F.; Yednock, Bree K.; Shanks, Alan L.; Galloway, Aaron W. (August 2020, Philosophical Transactions of the Royal Society B: Biological Sciences)

   null (Ed.)

   Dungeness crabs ( Metacarcinus magister ) are ecologically and economically important in the coastal Northeast Pacific, yet relatively little is currently known about their feeding behaviour in the wild or their natural diet. Trophic biomarkers, such as fatty acids (FA), can be used to reveal trophic interactions. We used two feeding experiments to assess differences in FA composition of juvenile crabs fed different known foods to evaluate how they modify and integrate dietary FA into their own tissues and determine whether crab FA reflect diet changes over a six-week period. These experimental results were then compared with the FA signatures of wild caught juvenile crab with undetermined diets. We found that juvenile Dungeness crabs fed different foods assimilated dietary FA into their tissues and were distinct in their FA signatures when analysed with multivariate statistics. Experimentally fed juvenile crabs contained greater proportions of the most abundant long-chain polyunsaturated fatty acids (LCPUFA, >C20) than their foods. Crabs fed foods lacking in LCPUFA, particularly DHA (22:6 ω 3, docosahexaenoic acid), did not survive or grew slower than crabs fed other foods. This suggests that LCPUFA are physiologically important for this species and indicates biosynthesis of these FA does not occur or is not sufficient to meet their needs. This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids’. 

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