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Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis
Choline is an essential nutrient derived primarily from dietary phosphatidylcholine, and its deficiency causes steatohepatitis. Here, the authors show that intestinal Atp8b1 contributes to choline metabolism through lysoPC absorption and that its dysfunction causes choline deficiency and steatohepatitis.
- Ryutaro Tamura
- , Yusuke Sabu
- & Hisamitsu Hayashi
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| Open Access
Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring
The authors show that maternal high-fat diet influences offspring’s ovarian reserve through maternal-embryonic cross-talk in mice and that maternal vitamin B1 supplementation could rescue ovarian primordial follicle reserve in mouse offspring.
- Wen-Xiang Liu
- , Hai-Ning Liu
- & Teng Zhang
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Dynamic chromatin architecture of the porcine adipose tissues with weight gain and loss
Here the authors study diet-induced weight gain/loss to identify chromatin architectures in adipose tissue (AT) associated obesity in a pig model. They found parallels and species-specific regulatory elements in humans and pigs that underpin AT specialization.
- Long Jin
- , Danyang Wang
- & Mingzhou Li
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Lysosomal-associated protein transmembrane 5 ameliorates non-alcoholic steatohepatitis by promoting the degradation of CDC42 in mice
Non-alcoholic steatohepatitis (NASH) has received great attention due to its high incidence, but the underlying mechanism remains poorly understood. Here, the authors show LAPTM5 expression ameliorates NASH and can potentially serve as a biological marker indicative of NASH progression.
- Lang Jiang
- , Jing Zhao
- & Jiahong Xia
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Male reproductive traits are differentially affected by dietary macronutrient balance but unrelated to adiposity
We know that nutrition and obesity can impact male fertility, but specific dietary guidelines for men trying to conceive don’t exist. Here the authors show that diet composition is likely more important than body fat in influencing reproductive traits and each macronutrient has different impacts.
- A. J. Crean
- , S. Afrin
- & T. Pini
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N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model
Obesity and aging increase Alzheimer’s disease (AD) risk. Here, using an AD mouse model and high-fat diet, we suggest that immune exhaustion links the two risk factors, and identify a metabolite that can hasten immune dysfunction and memory deficit.
- Stefano Suzzi
- , Tommaso Croese
- & Michal Schwartz
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Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models
Time-restricted feeding (TRF) can prevent muscle function decline from obesogenic challenges. Here, the authors reveal that TRF improves muscle function through modulations of common and distinct pathways in diet- and genetic-induced obesity models.
- Christopher Livelo
- , Yiming Guo
- & Girish C. Melkani
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Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
Retinoids can act as transcriptional regulators to regulate cell proliferation, differentiation, and other processes. Here, the authors show that uncompromised vitamin A (retinoid) metabolism and signaling in alveolar lipofibroblasts, endothelial and epithelial cells are required to lessen the severity of an acute inflammatory challenge in adult mouse lungs.
- Igor O. Shmarakov
- , Galina A. Gusarova
- & William S. Blaner
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The gut microbiome and early-life growth in a population with high prevalence of stunting
Here, using metagenomics, the authors show that the gut microbiome of rural Zimbabwean infants undergoes programmed maturation that is unresponsive to sanitation and nutrition interventions but is strongly associated with maternal HIV infection and can moderately predict linear growth.
- Ruairi C. Robertson
- , Thaddeus J. Edens
- & Amee R. Manges
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| Open Access
A method for an unbiased estimate of cross-ancestry genetic correlation using individual-level data
Cross-ancestry genetic correlation can reveal differences in the genetic basis of traits between populations, but methods can be biased by ancestry-specific genetic architecture. Here, the authors present a method to for estimating cross-ancestry genetic correlations, accounting for ancestry-specific genetic architecture.
- Md. Moksedul Momin
- , Jisu Shin
- & S. Hong Lee
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The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction
Impaired liver metabolic function is related to mortality in severely malnourished children. Here the authors report a role for the tryptophan-NAD + pathway in reduced hepatic mitochondrial function and liver steatosis in a mouse model of severe malnutrition.
- Guanlan Hu
- , Catriona Ling
- & Robert H. J. Bandsma
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Article
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Pleiotropic genetic architecture and novel loci for C-reactive protein levels
Chronic inflammation and lipometabolism share many causal genes and possibly pathways. Here, the authors use a multi-trait GWAS approach to study shared genetic determinants of low-grade inflammation, measured by C-reactive protein (CRP), and closely linked lipid and metabolic pathways.
- Fotios Koskeridis
- , Evangelos Evangelou
- & Ioanna Tzoulaki
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Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia
Enterotoxigenic Escherichia coli infections have been linked to non-diarrheal sequelae however, the reasons for this are unclear. Here, the authors present an additional role of heat-labile toxin in disrupting the structure and function of intestinal epithelial cells.
- Alaullah Sheikh
- , Brunda Tumala
- & James M. Fleckenstein
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Vitamin C epigenetically controls osteogenesis and bone mineralization
For decades vitamin C’s primary function in bone has been attributed to its involvement in collagen synthesis. Here, the authors uncover that vitamin C’s central role in bone is to globally orchestrate osteogenesis via epigenetic mechanisms.
- Roman Thaler
- , Farzaneh Khani
- & Andre J. van Wijnen
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SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner
Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.
- Tatiana Dandolini Saccon
- , Felippe Mousovich-Neto
- & Marcelo A. Mori
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Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes
Fat distribution is associated with cardiometabolic disease, although it has been less well studied than overall obesity. In a multiancestry exome-sequencing study, the authors identified predicted loss-of-function mutations in INHBE associated with favorable fat distribution and protection from type 2 diabetes.
- Parsa Akbari
- , Olukayode A. Sosina
- & Luca A. Lotta
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Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
Here, the authors characterize gut viromes in a cohort of individuals with metabolic syndrome, which they find associated with a highly widespread family of gut bacteriophages they name Candidatus Heliusviridae.
- Patrick A. de Jonge
- , Koen Wortelboer
- & Hilde Herrema
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Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice
Exercise increases energy expenditure and suppresses obesity, but the effector mechanisms are not still unclear. Here the authors profile serum proteomics in exercised mice to find reduced parvalbumin levels that correlate with increased M2 macrophage and suppressed diet-induced obesity to hint parvalbumin as a potential therapy target against obesity.
- Shaojian Lin
- , Anke Zhang
- & Bing Luan
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Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration
Impaired mitochondrial function in liver tissue may contribute to the pathogenesis and disease progression of nonalcoholic fatty liver disease (NAFLD). Here the authors report that patients with obesity have lower mitochondrial capacity in adipose tissues but higher capacity in the liver, without overall associations to NAFLD severity, and that bariatric surgery increases hepatic mitochondrial respiration and mitochondrial biogenesis.
- Julie S. Pedersen
- , Marte O. Rygg
- & Flemming Dela
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Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice
Yogurt consumption is associated with health benefits, but underlying mechanisms are unknown. Here, the authors show in a mouse model that yogurt intake prevents obesity-linked insulin resistance and hepatic steatosis through shifting the gut microbiota and enhancing production of fermentation-derived branched chain hydroxy acids.
- Noëmie Daniel
- , Renato Tadeu Nachbar
- & André Marette
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Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition
Malnourished children experience a high burden of intestinal pathogens that exacerbate growth stunting, and preventing this pathogen overgrowth has proved challenging. Here the authors show that diet-specific bacterial crossfeeding contributes to the overgrowth of intestinal pathogens during child malnutrition.
- K. E. Huus
- , T. T. Hoang
- & B. B. Finlay
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| Open Access
Association between serum retinol and overall and cause-specific mortality in a 30-year prospective cohort study
Vitamin A, of which retinol is the major form in the circulation, is a determinant of human health but whether vitamin A status is associated with mortality is not well understood. Here the authors report that in a prospective observational analysis of 29 104 men, higher serum retinol associates with lower risk of overall and cause-specific mortality.
- Jiaqi Huang
- , Stephanie J. Weinstein
- & Demetrius Albanes
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Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality
Higher intake of dietary fiber and whole grains are associated with reduced risk of various diseases including some cancers. Here, the authors estimate reductions in liver cancer of 22% and 31% and chronic liver disease mortality of 56% and 63% associated with increased whole grain and dietary fiber intake, respectively.
- Xing Liu
- , Wanshui Yang
- & Xuehong Zhang
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Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy
Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.
- Allison L. Fisher
- , Veena Sangkhae
- & Elizabeta Nemeth
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Revealing the role of the human blood plasma proteome in obesity using genetic drivers
Blood circulating proteins reflect biological processes, thus providing insight into complex traits. Here the authors study the relationship between 1000 plasma proteins and body mass index (BMI), highlighting widespread proteome changes and causal relationships between BMI and specific proteins.
- Shaza B. Zaghlool
- , Sapna Sharma
- & Karsten Suhre
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Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism
Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model.
- Benjamin A. H. Jensen
- , Jacob B. Holm
- & Tor E. Lea
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Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes
Western diet is one of the major causes underlying diabetes, and the microbes residing in the gut playing a critical role in mediating the effects of diet. Here the authors utilize network analysis to discover two species of Lactobacilli decreased by western diet, which improve glucose metabolism and restore of hepatic mitochondria in mice.
- Richard R. Rodrigues
- , Manoj Gurung
- & Natalia Shulzhenko
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Autozygosity influences cardiometabolic disease-associated traits in the AWI-Gen sub-Saharan African study
The prevalence of cardiometabolic diseases (CMDs) is increasing rapidly across Africa. Here, the authors investigate autozygosity in CMD-associated traits in over 10,000 sub-Saharan African individuals, showing these traits are influenced by sex-specific inbreeding depression and environmental interactions.
- Francisco C. Ceballos
- , Scott Hazelhurst
- & Michèle Ramsay
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Activation of GCN2/ATF4 signals in amygdalar PKC-δ neurons promotes WAT browning under leucine deprivation
The browning of white adipose tissue has potential benefits on metabolic disorders, but the nutritional factors and neuronal signals that mediate browning remain incompletely understood. Here, the authors show that leucine deprivation can induce WAT browning via GCN2/ATF4 signaling in amygdalar PKC-δ neurons.
- Feixiang Yuan
- , Haizhou Jiang
- & Feifan Guo
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| Open Access
Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice
Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.
- Stephanie J. Alexopoulos
- , Sing-Young Chen
- & Kyle L. Hoehn
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| Open Access
TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh
Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. Here the authors found that TDP-43, a RNA-binding protein, is required for milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh mRNA stability.
- Limin Zhao
- , Hao Ke
- & Baowei Jiao
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| Open Access
Edematous severe acute malnutrition is characterized by hypomethylation of DNA
The edematous form of severe acute childhood malnutrition (ESAM) presents with more severe multi-organ dysfunction than non-edematous SAM (NESAM). Here the authors assess genome-wide DNA methylation in buccal cells of SAM children and find that ESAM is characterized by hypomethylation at genes associated with disorders of nutrition and metabolism, including fatty liver and diabetes.
- Katharina V. Schulze
- , Shanker Swaminathan
- & Neil A. Hanchard
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| Open Access
Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity
Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.
- Mercedes Dávalos-Salas
- , Magdalene K. Montgomery
- & John M. Mariadason
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| Open Access
Intergenerational inheritance of high fat diet-induced cardiac lipotoxicity in Drosophila
Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.
- Maria Clara Guida
- , Ryan Tyge Birse
- & Rolf Bodmer
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| Open Access
Predicting nutrient content of ray-finned fishes using phylogenetic information
Humans increasingly depend on seafood for nutrition, but nutrient content is unknown for the vast majority of fish species. Here, the authors use phylogenetic analyses and data imputation to predict the nutrient content of fish that are under-studied but that could be of future dietary importance.
- Bapu Vaitla
- , David Collar
- & Christopher D. Golden
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Article
| Open Access
ER-associated ubiquitin ligase HRD1 programs liver metabolism by targeting multiple metabolic enzymes
HRD1 is an E3 ligase known to play a role in targeting degradation of misfolded proteins in the ER. Here the authors show that HRD1 interacts with metabolic enzymes and its liver specific deficiency results in lower body weight, blood glucose and plasma lipids during high fat diet in mice.
- Juncheng Wei
- , Yanzhi Yuan
- & Deyu Fang
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Article
| Open Access
Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat
FGF21 has a number of beneficial metabolic effects. Here, Li et al. show that FGF21 promotes the healthy expansion of subcutaneous white adipose tissue, promoting the healthy expansion of fat tissue as a regulatory mechanism to maintain systemic insulin sensitivity during nutrient excess.
- Huating Li
- , Guangyu Wu
- & Weiping Jia
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Article
| Open Access
Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator
Although many genetic variants are known for obesity, their function remains largely unknown. Here, in a weight-loss intervention cohort, the authors identify protein quantitative trait loci associated with BMI at baseline and after weight loss and find FAM46A to be a regulator of leptin in adipocytes.
- Jérôme Carayol
- , Christian Chabert
- & Jörg Hager
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Article
| Open Access
Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation
VLDLR regulates cellular lipoprotein uptake and storage. Here, the authors show that VLDLR, expressed on adipose tissue macrophages, is upregulated in obesity and promotes adipose tissue inflammation by upregulating ceramide production and facilitating M1-like macrophage polarization.
- Kyung Cheul Shin
- , Injae Hwang
- & Jae Bum Kim
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Article
| Open Access
MANF regulates hypothalamic control of food intake and body weight
MANF is a neurotrophic factor that is secreted but also mediates the unfolded protein response acting intracellularly. Here, the authors show that MANF expression in the brain is influenced by nutritional cues, and hypothalamic MANF influences food intake and systemic energy homeostasis.
- Su Yang
- , Huiming Yang
- & Xiao-Jiang Li
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Article
| Open Access
CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors
Adipose tissue contains macrophages that can influence both local and systemic metabolism via the secretion of cytokines. Here, Nawaz et al. report that M2-like macrophages, present in adipose tissue, create a microenvironment that inhibits proliferation of adipocyte progenitors due to the secretion of TGF-β1
- Allah Nawaz
- , Aminuddin Aminuddin
- & Kazuyuki Tobe
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| Open Access
Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model
Environmental enteropathy is a disorder of the small intestine that contributes to the persistence of childhood malnutrition worldwide. Here, Brownet al. show in mice that early-life malnourishment, in combination with exposure to commensal bacteria, remodels the small intestine to resemble features of the disease.
- Eric M. Brown
- , Marta Wlodarska
- & B. Brett Finlay
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Article
| Open Access
Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status
Gut microbes are known to influence whole-body metabolism. Here Everard et al.show the adaptor protein MyD88 in intestinal epithelial cells is sensitive to changes in the diet and affects composition of the gut microbiota, which influences the development of obesity and associated diseases.
- Amandine Everard
- , Lucie Geurts
- & Patrice D. Cani
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Berberine activates thermogenesis in white and brown adipose tissue
Berberine is contained in some plant-derived medicines and is known to have anti-diabetic effects. Here the authors show that berberine activates thermogenesis in white and brown adipose tissues, thereby increasing organismal energy expenditure and limiting weight gain in genetically obese mice.
- Zhiguo Zhang
- , Huizhi Zhang
- & Guang Ning
Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders