Impact of non-sugar sweeteners on metabolism beyond sweet taste perception.

Non-sugar sweeteners (NSS), low- or no-calorie alternatives to sugar, are marketed for weight loss and improved blood glucose control in people with diabetes. However, their health effects remain controversial. This review provides a brief overview of sweet taste perception and summarizes experimental findings of the impact of NSS on cardiometabolic health in animal models and humans.

The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.

Aicardi-Goutières syndrome (AGS) is a progressive genetic encephalopathy caused by pathogenic mutations in genes controlling cellular anti-viral responses and nucleic acid metabolism. The mutations initiate autoinflammatory processes in the brain and systemically that are triggered by chronic overproduction of type I interferon (IFN), including IFN-alpha. Emerging disease-directed therapies aim to dampen autoinflammation and block cellular responses to IFN production, creating an urgent and unmet need to understand better which cells, compartments, and mechanisms underlying disease pathogenesis.

Eating disorder risk among Australian youth starting a diet in the community.

Dieting is a potent risk factor for eating disorder (ED) symptoms and development, which typically occur in late adolescence. However, as diets are often motivated by body image concerns (another core ED risk factor), dieters may already carry heightened ED risk. Thus, the current study aimed to document ED risk among young people starting a diet in the community.

On the pathogenesis of obesity: causal models and missing pieces of the puzzle.

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century.

Diet modifies the association between alcohol consumption and severe alcohol-related liver disease incidence.

It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants.

Vitamin B5 is a context-dependent dietary regulator of nociception.

Chronic pain has an enormous impact on the quality of life of billions of patients, families, and caregivers worldwide. Current therapies do not adequately address pain for most patients. A basic understanding of the conserved genetic framework controlling pain may help us develop better, non-addictive pain therapies.

Increased intake of tree forage by moose is associated with intake of crops rich in nonstructural carbohydrates.

Animals representing a wide range of taxonomic groups are known to select specific food combinations to achieve a nutritionally balanced diet. The nutrient balancing hypothesis suggests that, when given the opportunity, animals select foods to achieve a particular target nutrient balance, and that balancing occurs between meals and between days. For wild ruminants who inhabit landscapes dominated by human land use, nutritionally imbalanced diets can result from ingesting agricultural crops rich in starch and sugar (nonstructural carbohydrates [NCs]), which can be provided to them by people as supplementary feeds.

Paternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring.

Paternal diet can influence the phenotype of the next generation, yet, the dietary components inducing specific responses in the offspring are not identified. Here, we use the Nutritional Geometry Framework to determine the effects of pre-conception paternal dietary macronutrient balance on offspring metabolic and behavioral traits in mice. Ten isocaloric diets varying in the relative proportion of protein, fats, and carbohydrates are fed to male mice prior to mating.

Fungal infection alters collective nutritional intake of ant colonies.

In animals, parasitic infections impose significant fitness costs. Infected animals can alter their feeding behavior to resist infection, but parasites can manipulate animal foraging behavior to their own benefits. How nutrition influences host-parasite interactions is not well understood, as studies have mainly focused on the host and less on the parasite.

Towards an integrated understanding of dietary phenotypes.

Diet and nutrition comprise a complex, multi-faceted interface between animal biology and food environments. With accumulating information on the many facets of this association arises a need for systems-based approaches that integrate dietary components and their links with ecology, feeding, post-ingestive processes and the functional and ecological consequences of these interactions. We briefly show how a modelling approach, nutritional geometry, has used the experimental control afforded in laboratory studies to begin to unravel these links.

Protein appetite as an integrator in the obesity system: the protein leverage hypothesis.

Despite the large volume and extensive range of obesity research, there is substantial disagreement on the causes and effective preventative strategies. We suggest the field will benefit from greater emphasis on integrative approaches that examine how various potential contributors interact, rather than regarding them as competing explanations. We demonstrate the application of nutritional geometry, a multi-nutrient integrative framework developed in the ecological sciences, to obesity research.

Normal diet ameliorates obesity more safely and effectively than ketogenic diet does in high-fat diet-induced obesity mouse based on gut microbiota and lipid metabolism.

Growing evidence supports the efficacy of ketogenic diets for inducing weight loss, but there are also potential health risks due to their unbalanced nutrient composition. We aim at assessing relative effectiveness of a balanced diet and ketogenic diet for reversing metabolic syndrome in a diet-induced C57BL/6J mouse model. Mice were fed high-fat diet to induce obesity.

An immunomodulating peptide to counteract solar radiation-induced immunosuppression and DNA damage.

Ultraviolet radiation (UVR) induces immunosuppression and DNA damage, both of which contribute to the rising global incidence of skin cancer including melanoma. Nucleotide excision repair, which is activated upon UVR-induced DNA damage, is linked to expression of interleukin-12 (IL-12) which serves to limit immunosuppression and augment the DNA repair process. Herein, we report an immunomodulating peptide, designated IK14800, that not only elicits secretion of IL-12, interleukin-2 (IL-2) and interferon-gamma (IFN-γ) but also reduces DNA damage in the skin following exposure to UVR.

Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway.

Dietary restriction induces a sexually dimorphic type I interferon response in mice with gene-environment interactions.

Intermittent fasting (IF) is an established intervention to treat the growing obesity epidemic. However, the interaction between dietary interventions and sex remains a significant knowledge gap. In this study, we use unbiased proteome analysis to identify diet-sex interactions.

How molecular techniques are developed from natural systems.

A striking characteristic of the molecular techniques of genetics is that they are derived from natural occurring systems. RNA interference, for example, utilizes a mechanism that evolved in eukaryotes to destroy foreign nucleic acid. Other case studies I highlight are restriction enzymes, DNA sequencing, polymerase chain reaction, gene targeting, fluorescent proteins (such as, green fluorescent protein), induced pluripotent stem cells, and clustered regularly interspaced short palindromic repeats-CRISPR associated 9.

Male reproductive traits are differentially affected by dietary macronutrient balance but unrelated to adiposity.

Dietary factors influence male reproductive function in both experimental and epidemiological studies. However, there are currently no specific dietary guidelines for male preconception health. Here, we use the Nutritional Geometry framework to examine the effects of dietary macronutrient balance on reproductive traits in C57BL/6 J male mice.

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria.

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection.

Biosynthetic constraints on amino acid synthesis at the base of the food chain may determine their use in higher-order consumer genomes.

Dietary nutrient composition is essential for shaping important fitness traits and behaviours. Many organisms are protein limited, and for Drosophila melanogaster this limitation manifests at the level of the single most limiting essential Amino Acid (AA) in the diet. The identity of this AA and its effects on female fecundity is readily predictable by a procedure called exome matching in which the sum of AAs encoded by a consumer's exome is used to predict the relative proportion of AAs required in its diet.

Increased Levels of the Parkinson's Disease-Associated Gene ITPKB Correlate with Higher Expression Levels of α-Synuclein, Independent of Mutation Status.

Autosomal dominant mutations in the gene encoding α-synuclein () were the first to be linked with hereditary Parkinson's disease (PD). Duplication and triplication of has been observed in PD patients, together with mutations at the N-terminal of the protein, among which A30P and A53T influence the formation of fibrils. By overexpressing human α-synuclein in the neuronal system of , we functionally validated the ability of , an ortholog of the GWAS identified risk gene, Inositol-trisphosphate 3-kinase B (), to modulate α-synuclein toxicity in vivo.

Persistent nociceptor hyperactivity as a painful evolutionary adaptation.

Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive.

Stone tools improve diet quality in wild monkeys.

Tool use is a fundamental feature of human evolution. Stone tools are in the archaeological record from 3.4 Ma, even before Homo, and the use of stone tools probably predated the split between hominins and panins.

Homolog of the Human Carpenter Syndrome Linked Gene, , Is Required for Synapse Development and Function.

multiple epidermal growth factor-like domains 8 (dMegf8) is a homolog of human encodes a multidomain transmembrane protein which is highly conserved across species. In humans, mutations cause a rare genetic disorder called Carpenter syndrome, which is frequently associated with abnormal left-right patterning, cardiac defects, and learning disabilities. is also associated with psychiatric disorders.