Botanical Interventions to Improve Glucose Control and Options for Diabetes Therapy.

Diabetes mellitus is a major public health problem worldwide. This endocrine disease is clustered into distinct subtypes based on the route of development, with the most common forms associated with either autoimmunity (T1DM) or obesity (T2DM). A shared hallmark of both major forms of diabetes is a reduction in function (insulin secretion) or mass (cell number) of the pancreatic islet beta-cell.

A Randomized Controlled Trial to Address Consumer Food Waste with a Technology-aided Tailored Sustainability Intervention.

There is growing concern whether pro-environmental behavioral interventions can generate sufficient reductions in carbon emissions to address climate change. While many have suggested enhanced tailoring of interventions to increase effect sizes, and while individual tailoring is common among health interventions, little is known about how individual tailoring may impact effect sizes for pro-environmental behavioral interventions. Using a novel technology-aided delivery and measurement approach, we conduct a randomized controlled trial featuring an individually tailored intervention focused on reducing the amount of food wasted by participants over approximately one week in their normal living conditions.

Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta.

Adverse exposures during pregnancy have been shown to contribute to susceptibility for chronic diseases in offspring. Maternal diabetes during pregnancy is associated with higher risk of pregnancy complications, structural birth defects, and cardiometabolic health impairments later in life. We showed previously in a mouse model that the placenta is smaller in diabetic pregnancies, with reduced size of the junctional zone and labyrinth.

The Nuanced Metabolic Functions of Endogenous FGF21 Depend on the Nature of the Stimulus, Tissue Source, and Experimental Model.

Fibroblast growth factor 21 (FGF21) is a hormone that is involved in the regulation of lipid, glucose, and energy metabolism. Pharmacological FGF21 administration promotes weight loss and improves insulin sensitivity in rodents, non-human primates, and humans. However, pharmacologic effects of FGF21 likely differ from its physiological effects.

An estrogen-sensitive hypothalamus-midbrain neural circuit controls thermogenesis and physical activity.

Estrogen receptor–α (ERα) expressed by neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (ERα) regulates body weight in females, but the downstream neural circuits mediating this biology remain largely unknown. Here we identified a neural circuit mediating the metabolic effects of ERα neurons. We found that selective activation of ERα neurons stimulated brown adipose tissue (BAT) thermogenesis, physical activity, and core temperature and that ERα neurons provide monosynaptic glutamatergic inputs to 5-hydroxytryptamine (5-HT) neurons in the dorsal raphe nucleus (DRN).

Emergence of the obesity epidemic: 6-decade visualization with humanoid avatars.

Background: Visualizations of the emerging obesity epidemic, such as with serial US color prevalence maps, provide graphic images that extend informative public health messages beyond those in written communications. Advances in low-cost 3D optical technology now allow for development of large image databases that include participants varying in race/ethnicity, body mass, height, age, and circumferences. When combined with contemporary statistical methods, these data sets can be used to create humanoid avatar images with prespecified anthropometric features.

Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum.

Agouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase () in mice. We hypothesised that metabolic sensing in AgRP neurons is required to increase motivation for food reward by modulating accumbal or striatal dopamine release.

Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.

Importance: Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.

Objective: To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.

Obesity, Body Composition, and Sex Hormones: Implications for Cardiovascular Risk.

Cardiovascular disease (CVD) continues to be the leading cause of death in adults, highlighting the need to develop novel strategies to mitigate cardiovascular risk. The advancing obesity epidemic is now threatening the gains in CVD risk reduction brought about by contemporary pharmaceutical and surgical interventions. There are sex differences in the development and outcomes of CVD; premenopausal women have significantly lower CVD risk than men of the same age, but women lose this advantage as they transition to menopause, an observation suggesting potential role of sex hormones in determining CVD risk.

Broad spectrum of CRISPR-induced edits in an embryonic lethal gene.

Mendelian genetics poses practical limitations on the number of mutant genes that can be investigated simultaneously for their roles in embryonic development in the mouse. While CRISPR-based gene editing of multiple genes at once offers an attractive alternative strategy, subsequent breeding or establishment of permanent mouse lines will rapidly segregate the different mutant loci again. Direct phenotypic analysis of genomic edits in an embryonic lethal gene in F0 generation mice, or F0 mouse embryos, circumvents the need for breeding or establishment of mutant mouse lines.

Overfeeding-induced weight gain elicits decreases in sex hormone-binding globulin in healthy males-Implications for body fat distribution.

Objective: Obesity and upper-body fat elevates cardiometabolic risk. However, mechanisms predisposing to upper-body fat accumulation are not completely understood. In males, low testosterone (T) frequently associates with obesity, and estrogen deficiency may contribute to upper-body adiposity.

Organization of sympathetic innervation of interscapular brown adipose tissue in the mouse.

The interscapular brown adipose tissue (iBAT) is under sympathetic control, and recent studies emphasized the importance of efferent sympathetic and afferent sensory or humoral feedback systems to regulate adipose tissue function and overall metabolic health. However, functional studies of the sympathetic nervous system in the mouse are limited, because details of anatomy and fine structure are lacking. Here, we used reporter mice for tyrosine hydroxylase expressing neurons (TH:tomato mice), iDISCO tissue clearance, confocal, lightsheet, and electron microscopy to clarify that (a) iBAT receives sympathetic input via dorsal rami (instead of often cited intercostal nerves); (b) dorsal rami T1-T5 correspond to the postganglionic input from sympathetic chain ganglia (stellate/T1-T5); (c) dorsal rami serve as conduits for sympathetic axons that branch off in finer nerve bundles to enter iBAT; (d) axonal varicosities show strong differential innervation of brown (dense innervation) versus white (sparse innervation) adipocytes, that surround the core iBAT in the mouse and are intermingled in human adipose tissues, (e) axonal varicosities can form neuro-adipocyte junctions with brown adipocytes.

Bioactive compounds from Artemisia dracunculus L. activate AMPK signaling in skeletal muscle.

An extract from Artemisia dracunculus L. (termed PMI-5011) improves glucose homeostasis by enhancing insulin action and reducing ectopic lipid accumulation, while increasing fat oxidation in skeletal muscle tissue in obese insulin resistant male mice. A chalcone, DMC-2, in PMI-5011 is the major bioactive that enhances insulin signaling and activation of AKT.

E-cigarette device and liquid characteristics and E-cigarette dependence: A pilot study of pod-based and disposable E-cigarette users.

Background: E-cigarette device and liquid characteristics, such as electrical power output and liquid nicotine concentration, determine the rate at which nicotine is emitted from the e-cigarette (i.e., nicotine flux), and thus are likely to influence user nicotine dependence.

Evaluation of Dietary Patterns and All-Cause Mortality: A Systematic Review.

Importance: The 2020 Dietary Guidelines Advisory Committee conducted a systematic review of existing research on diet and health to inform the current Dietary Guidelines for Americans. The committee answered this public health question: what is the association between dietary patterns consumed and all-cause mortality (ACM)?

Objective: To ascertain the association between dietary patterns consumed and ACM.

Evidence Review: Guided by an analytical framework and predefined inclusion and exclusion criteria developed by the committee, the US Department of Agriculture's Nutrition Evidence Systematic Review (NESR) team searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase and dual-screened the results to identify articles that were published between January 1, 2000, and October 4, 2019.

Meal composition during an ad libitum buffet meal and longitudinal predictions of weight and percent body fat change: The role of hyper-palatable, energy dense, and ultra-processed foods.

Background: Foods that increase obesity risk are ubiquitous in the US food environment. Such foods may be the target of hedonic eating, which may facilitate weight gain and lead to obesity. The study tested whether meal composition during an ad libitum buffet meal was associated with 1-year weight and percent body fat changes among healthy younger adults without obesity.

Sympathetic innervation of the mouse kidney and liver arising from prevertebral ganglia.

The sympathetic nervous system (SNS) plays a crucial role in the regulation of renal and hepatic functions. Although sympathetic nerves to the kidney and liver have been identified in many species, specific details are lacking in the mouse. In the absence of detailed information of sympathetic prevertebral innervation of specific organs, selective manipulation of a specific function will remain challenging.

Learning of food preferences: mechanisms and implications for obesity & metabolic diseases.

Omnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods.

Sympathetic Innervation of White Adipose Tissue: to Beige or Not to Beige?

Obesity research progresses in understanding neuronal circuits and adipocyte biology to regulate metabolism. However, the interface of neuro-adipocyte interaction is less studied. We summarize the current knowledge of adipose tissue innervation and interaction with adipocytes and emphasize adipocyte transitions from white to brown adipocytes and vice versa.

Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding.

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake.

The effects of the form of sugar (solid vs. beverage) on body weight and fMRI activation: A randomized controlled pilot study.

Objective: To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and reward processing in the brain.

Methods: In a single blind randomized controlled pilot trial (RCT), twenty participants with BMI between 20 and 40 kg/m2 were randomized to consume a 20 fluid ounce soda (SSB, 248 kcal) or the equivalent in solid form (SSS; similar to thick gelatin or gummy candy) daily. At baseline and day 28, fasting body weight and fed-state BOLD fMRI of the brain were assessed.

IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). This increase is closely associated with insulin sensitization.

Prenylated Coumaric Acids from Beneficially Modulate Adipogenesis.

Two new diprenylated coumaric acid isomers ( and ) and two known congeners, capillartemisin A () and B (), were isolated from as bioactive markers using bioactivity-guided HPLC fractionation. Their structures were determined by spectroscopic means, including 1D and 2D NMR methods and LC-MS, with their purity assessed by 1D H pure shift qNMR spectroscopic analysis. The bioactivity of compounds was evaluated by enhanced accumulation of lipids, as measured using Oil Red O staining, and by increased expression of several adipocyte marker genes, including adiponectin in 3T3-L1 adipocytes relative to untreated negative controls.

Physiology of Energy Intake in the Weight-Reduced State.

Physiological adaptations to intentional weight loss can facilitate weight regain. This review summarizes emerging findings on hypothalamic and brainstem circuitry in the regulation of body weight and identifies promising areas for research to improve therapeutic interventions for sustainable weight loss. There is good evidence that body weight is actively regulated in a homeostatic fashion similar to other physiological parameters.

Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.

Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.

Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.