FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Objective: Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences.

Methods And Results: In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice.

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice.

FGF21 as a mediator of adaptive changes in food intake and macronutrient preference in response to protein restriction.

Free-feeding animals navigate complex nutritional landscapes in which food availability, cost, and nutritional value can vary markedly. Animals have thus developed neural mechanisms that enable the detection of nutrient restriction, and these mechanisms engage adaptive physiological and behavioral responses that limit or reverse this nutrient restriction. This review focuses specifically on dietary protein as an essential and independently defended nutrient.

Altered Estrous Cyclicity and Feeding Neurocircuitry, but Not Cardiovascular Indices in Female Offspring from Dams with Previous Vertical Sleeve Gastrectomy Surgery.

Metabolic syndrome (MetS), which includes obesity, diabetes, hypertension, hyperlipidemia, and fatty-liver disease, affects more than two-thirds of the U.S. population.

FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice.

Dietary protein restriction is increasingly recognized as a unique approach to improve metabolic health, and there is increasing interest in the mechanisms underlying this beneficial effect. Recent work indicates that the hormone FGF21 mediates the metabolic effects of protein restriction in young mice. Here we demonstrate that protein restriction increases lifespan, reduces frailty, lowers body weight and adiposity, improves physical performance, improves glucose tolerance, and alters various metabolic markers within the serum, liver, and adipose tissue of wildtype male mice.

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.

Protein Appetite at the Interface between Nutrient Sensing and Physiological Homeostasis.

Feeding behavior is guided by multiple competing physiological needs, as animals must sense their internal nutritional state and then identify and consume foods that meet nutritional needs. Dietary protein intake is necessary to provide essential amino acids and represents a specific, distinct nutritional need. Consistent with this importance, there is a relatively strong body of literature indicating that protein intake is defended, such that animals sense the restriction of protein and adaptively alter feeding behavior to increase protein intake.

Leptin receptor signaling is required for intact hypoglycemic counterregulation: A study in male Zucker rats.

Hypoglycemia is a major barrier to clinical management of persons with diabetes. Emerging evidence supports a role for leptin in gating hypoglycemic counterregulation. This work demonstrates that male leptin receptor null, Zucker (fa/fa), rats display severe impairments in hypoglycemic counterregulation.

Dysregulated appetitive leptin signaling in male rodent offspring from post-bariatric dams.

Bariatric surgery produces significant positive benefits to recipients such as significant body fat loss and resolution of the various obesity-related comorbidities, such as reduced reproductive function. Females of childbearing age seek bariatric surgical remedies to improve their chance of successful pregnancy; however, limited knowledge exists on the impact of surgical weight loss to subsequently born offspring. We previously reported that circulating leptin levels were reduced in pregnant females having previously received vertical sleeve gastrectomy (VSG) in comparison to control dams having received Sham surgery.

Ghrelin signalling is dysregulated in male but not female offspring in a rat model of maternal vertical sleeve gastrectomy.

Bariatric surgery is the most effective and durable means of treating obesity and its comorbidities. Women make up 80% of those receiving weight loss surgery and they experience improvements in fertility. Unfortunately, bariatric surgery in the context of pregnancy is associated with complications, including growth restriction and small-for-gestational age offspring (SGA).

Curbing Obesity from One Generation to Another: the Effects of Bariatric Surgery on the In Utero Environment and Beyond.

Approximately 250,000 individuals seek bariatric surgery each year in the USA for the long-term resolution of obesity-related comorbidities. Greater than 80% of these individuals are women and approximately half are of child-bearing age. Although there are many positive metabolic benefits that are realized through surgical weight loss for both men and women, the various long-term hormonal, molecular, nutrient, and epigenetic changes following bariatric surgery have not been evaluated for the surgical recipient or in the context of pregnancy and the offspring.

Immuno-hematologic parameters following rodent spinal cord contusion are negatively influenced by high-fat diet consumption.

Spinal cord injury (SCI) results in perturbations to the immune system leading to increased infection susceptibility. In parallel, the consumption of high-fat diets (HFD) leads to a chronic inflammation in circulation and body tissues. We investigated the impact of 16 weeks of HFD on chronically-injured rats.

Altered immune system in offspring of rat maternal vertical sleeve gastrectomy.

Obesity in women results in reduced fertility and increased complications during pregnancy. Vertical sleeve gastrectomy (VSG) effectively reduces weight, type 2 diabetes, and dyslipidemia, but is also associated with preterm and small-for-gestational age births. The mechanism by which VSG influences fetal development remains unknown.

Splenectomy fails to attenuate immuno-hematologic changes after rodent vertical sleeve gastrectomy.

Unlabelled: Bariatric surgery is on the rise for long-term weight loss and produces various positive metabolic health benefits. The mechanisms that produce surgical weight loss are not yet fully understood. Previous studies showed vertical sleeve gastrectomy prior to gestation resulted in reduced peripheral blood lymphocytes measured during pregnancy due to an undetermined etiology.

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

Bariatric surgery is increasingly employed to improve fertility and reduce obesity-related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism, and other gestational disorders.

Chronic spinal cord changes in a high-fat diet-fed male rat model of thoracic spinal contusion.

Individuals that suffer injury to the spinal cord can result in long-term, debilitating sequelae. Spinal cord-injured patients have increased risk for the development of metabolic disease, which can further hinder the effectiveness of treatments to rehabilitate the cord and improve quality of life. In the present study, we sought to understand the impact of high-fat diet (HFD)-induced obesity on spinal cord injury (SCI) by examining transcriptome changes in the area of the injury and rostral and caudal to site of damage 12 wk after injury.

Vertical sleeve gastrectomy improves indices of metabolic disease in rodent model of surgical menopause.

Objective: Although women are the most common recipients of weight loss surgeries for the amelioration of the comorbidities of obesity, few studies have addressed the efficacy of these procedures with specific attention to reproductive stage. Here we ask in a rodent model of vertical sleeve gastrectomy (VSG) whether improvements to metabolic health are realized in women having received surgical menopause. Specifically we were interested in knowing whether rats made menopausal through surgical means would exhibit persistent hepatic steatosis as reported in previously pregnant, freely cycling female VSG rats or if it is resolved as reported in male VSG rats.