Altered Energy Balance Research Articles

The relationship between Marriage and Body Mass Index in China：Evidence from the China Health and Nutrition Survey

This study investigates the impact of marriage on the body mass index (BMI) of individuals aged 18–45 in China. We used data from ten rounds of the China Health and Nutrition Survey spanning from 1989 to 2015, and applied Difference-in-Differences (DID) model to examine the impact of marriage on BMI. Our findings reveal that marriage has a significant positive effect on BMI, especially among males, with post-marriage elevation of male BMI continuing to increase over time. Moreover, marriage is associated with a 5.2% increase in the prevalence of overweight and a 2.5% rise in the incidence of obesity among males. While energy intake levels for Chinese women did not undergo significant changes after marriage, nor did their energy expenditure levels, men experienced a marked alteration in energy balance, characterized by an increase in caloric intake and a decrease in physical activity. Furthermore, our study confirms significant period differences in the effect of marriage on BMI, with post-marriage elevation of male BMI continuing to rise over time. In contrast, there was no clear trend for female BMI after marriage. Our research highlights the importance of promoting physical fitness and health management within families while fostering intimate relationships through marriage. Public health policies should consider the potential impact of marriage as an intervention window for addressing individuals' weight management needs. Distinct post-marriage body management plans should be designed for both genders.

Effect and mechanism of GPR75 in metabolic dysfunction-related steatosis liver disease.

Research on G protein-coupled receptor 75 (GPR75) in metabolic dysfunction-related steatosis liver disease (MASLD) reveals its potential role in regulating body weight and energy balance. Loss-of-function mutations in the GPR75 gene are significantly associated with lower body mass index and reduced body weight. Studies demonstrate that GPR75 knockout mice exhibit lower fasting blood glucose levels, improved glucose homeostasis, and significant prevention of high-fat diet-induced MASLD. The absence of GPR75 reduces fat accumulation by beneficially altering energy balance rather than restricting adipose tissue expansion. Moreover, female GPR75 knockout mice show greater protection against lipid accumulation on a high-fat diet compared to males, potentially attributed to higher physical activity and energy expenditure. However, current research primarily relies on mouse models, and its applicability to humans requires further validation. Future studies should explore the role of GPR75 across diverse populations, its clinical potential, and delve into its specific mechanisms and interactions with other metabolic pathways. Ultimately, targeted therapies based on GPR75 could offer novel strategies for the prevention and treatment of MASLD and other metabolic disorders.

Environmental chemicals change extracellular lipidome of mature human white adipocytes

Certain environmental chemicals affect the body's energy balance and are known as metabolism disrupting chemicals (MDCs). MDCs have been implicated in the development of metabolic diseases, such as obesity and type 2 diabetes. In contrast to their well-known impact on developing adipocytes, MDC effects leading to altered energy balance and development of insulin resistance in mature white adipocytes, constituents of adult adipose tissue, are largely unclear.Here, we investigated the effects of six well-established environmental MDCs (bisphenol A (BPA), perfluorooctanoic acid (PFOA), triclosan (TCS), p,p-dichlorodiphenyl-dichloroethylene (ppDDE), tributyltin chloride (TBT) and triphenyl phosphate (TPP)) on mature human white adipocytes derived from mesenchymal stem cells in vitro. We aimed to identify biomarkers and sensitive endpoints of their metabolism disrupting effects. While most of the tested exposures had no effect on adipocyte glucose consumption, lipid storage and assessed gene expression endpoints, the highest concentration of triclosan affected the total lipid storage and adipocyte size, as well as glucose consumption and mRNA expression of the glucose transporter GLUT1, leptin and adiponectin. Additionally, an increased expression of adiponectin was observed with TPP and the positive control PPARγ agonist rosiglitazone.In contrast, the lipidomic analysis of the cell culture medium after a 3-day exposure was extremely sensitive and revealed concentration-dependent changes in the extracellular lipidome of adipocytes exposed to nearly all studied chemicals. While some of the extracellular lipidome changes were specific for the MDC used, some effects were found common to several tested chemicals and included increases in lysophosphatidylcholines, glycerophospholipids and ceramides and a decrease in fatty acids, with possible implications in inflammation, lipid and glucose uptake.This study points to early signs of metabolic disruption and likely systemic effects of mature adipocyte exposure to environmental chemicals, as well as to the need to include lipidomic endpoints in the assessment of adverse effects of MDCs.

Alterations in energy balance and the antioxidant system due to heat stress: focus on animal production

In areas where the ambient temperature is above the thermoneutral zone, the economic loss from animals for human consumption, such as pigs, is worrying. Heat Stress (HS) increases body temperature and causes a subsequent reduction in feed intake. This reduction results in the loss of essential nutrients, such as amino acids, which are crucial for growth rate and the activation of vital biochemical mechanisms. However, the effects of HS on reactive oxygen species (ROS) generation, and the activation of mechanisms such as the antioxidant system associated with nuclear factor erythroid-derived 2-like-2 (Nrf2), energy balance, protein synthesis and mitochondrial biogenesis have received limited attention. In this work, we provide a comprehensive review of the existing evidence regarding the significance of nutritional components and their association with HS. We particularly emphasize ROS generation, mitochondrial alterations, and the activation of Nrf2, AMP-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR) signaling pathways in response to the disruption of homeostasis.

Role of AMP Deaminase in Mucor circinelloides: Implications for Nitrogen Utilization and Lipid Biosynthesis.

Lipid accumulation in oleaginous organisms is initiated by AMP deaminase (AMPD) after nitrogen depletion because it mediates the concentration of intracellular adenosine monophosphate (AMP). However, the role of AMPD in lipogenesis in the oleaginous fungus Mucor circinelloides is largely unknown. Therefore, we identified the genes (ampd1 and ampd2) encoding AMPD and investigated the role of AMPD in lipid synthesis in this fungus by overexpressing and deleting ampd genes. Deletion of ampd1 and ampd2 caused 21 and 28% increments in lipid contents under N-limited conditions, respectively. These increases were correlated with the activation of enzymes involved in lipogenesis and the alteration of energy balance. Unexpectedly, overexpression of ampd genes affected nitrogen consumption in both N-limited and N-excess media, which resulted in an increase in cell growth and lipid accumulation compared with the control strain when nitrogen was available. Furthermore, the increased lipid accumulation in the ampd-overexpressing mutants in N-excess media was accompanied by enhanced activities of lipid biosynthetic enzymes. These data suggested that nitrogen metabolism and energy metabolism are affected by AMPD, and overexpression of ampd genes induced lipid accumulation under nitrogen-rich conditions by mimicking the nitrogen limitation response. This highlights an intriguing function of AMPD in M. circinelloides.

No evidence that the widespread environmental contaminant caffeine alters energy balance or stress responses in fish

AbstractAnthropogenic sources of environmental pollution are ever‐increasing as urban areas expand and more chemical compounds are used in daily life. The stimulant caffeine is one of the most consumed chemical compounds worldwide, and as a result, has been detected as an environmental contaminant in all types of major water sources on all continents. Exposure of wildlife to environmental pollutants can disrupt the energy balance of these organisms, as restoration of homeostasis is prioritised. In turn, energy allocated to other key biological processes such as growth or reproduction may be affected, consequently reducing the overall fitness of an individual. Therefore, we aimed to investigate if long‐term exposure to environmentally relevant concentrations of caffeine had any energetic consequences on wildlife. Specifically, we exposed wild eastern mosquitofish (Gambusia holbrooki) to one of three nominal concentrations of caffeine (0, 100 and 10,000 ng/L) and assayed individuals for metabolic rate, general activity, antipredator and foraging behaviour and body size as measures of energy expenditure or energy intake. We found no differences in any measured traits between any of the given exposure treatments, indicating that exposure to caffeine at current environmental levels may not adversely affect the energy balance and fitness of vulnerable freshwater fish.

Adiponectin Modulates Smooth Muscle Cell Morpho-Functional Properties in Murine Gastric Fundus via Sphingosine Kinase 2 Activation.

Adipokines are peptide hormones produced by the adipose tissue involved in several biological functions. Among adipokines, adiponectin (ADPN) has antidiabetic and anti-inflammatory properties. It can also modulate food intake at central and peripheral levels, acting on hypothalamus and facilitating gastric relaxation. ADPN exerts its action interacting with two distinct membrane receptors and triggering some well-defined signaling cascades. The ceramidase activity of ADPN receptor has been reported in many tissues: it converts ceramide into sphingosine. In turn, sphingosine kinase (SK) phosphorylates it into sphingosine-1 phosphate (S1P), a crucial mediator of many cellular processes including contractility. Using a multidisciplinary approach that combined biochemical, electrophysiological and morphological investigations, we explored for the first time the possible role of S1P metabolism in mediating ADPN effects on the murine gastric fundus muscle layer. By using a specific pharmacological inhibitor of SK2, we showed that ADPN affects smooth muscle cell membrane properties and contractile machinery via SK2 activation in gastric fundus, adding a piece of knowledge to the action mechanisms of this hormone. These findings help to identify ADPN and its receptors as new therapeutic targets or as possible prognostic markers for diseases with altered energy balance and for pathologies with fat mass content alterations.

Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis

ObjectiveThe activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. The activation of NST however is extremely temporal and the mechanisms surrounding how the benefits of NST are sustained once fully activated, remain unexplored. The objective of this study is to investigate the role of 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) in NST maintenance, which is a critical regulator identified in this study. MethodsThe expression of Nipsnap1 was profiled by immunoblotting and RT-qPCR. We generated Nipsnap1 knockout mice (N1–KO) and investigated the function of Nipsnap1 in NST maintenance and whole-body metabolism using whole body respirometry analyses. We evaluate the metabolic regulatory role of Nipsnap1 using cellular and mitochondrial respiration assay. ResultsHere, we show Nipsnap1 as a critical regulator of long-term thermogenic maintenance in brown adipose tissue (BAT). Nipsnap1 localizes to the mitochondrial matrix and increases its transcript and protein levels in response to both chronic cold and β3 adrenergic signaling. We demonstrated that these mice are unable to sustain activated energy expenditure and have significantly lower body temperature in the face of an extended cold challenge. Furthermore, when mice are exposed to the pharmacological β3 agonist CL 316, 243, the N1–KO mice exhibit significant hyperphagia and altered energy balance. Mechanistically, we demonstrate that Nipsnap1 integrates with lipid metabolism and BAT-specific ablation of Nipsnap1 leads to severe defects in beta-oxidation capacity when exposed to a cold environmental challenge. ConclusionOur findings identify Nipsnap1 as a potent regulator of long-term NST maintenance in BAT.

Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.

A vitamin D deficient diet increases weight gain and compromises bone biomechanical properties without a reduction in BMD in adult female mice

Vitamin D contributes to the development and maintenance of bone. Evidence suggests vitamin D status can also alter energy balance and gut health. In young animals, vitamin D deficiency (VDD) negatively affects bone mineral density (BMD) and bone microarchitecture, and these effects may also occur due to chronic ethanol intake. However, evidence is limited in mature models, and addressing this was a goal of the current study. Seven-month-old female C57BL/6 mice (n = 40) were weight-matched and randomized to one of four ad libitum diets: control, alcohol (Alc), vitamin D deficient (0 IU/d), or Alc+VDD for 8 weeks. A purified (AIN-93) diet was provided with water or alcohol (10 %) ad libitum. Body weight and food intake were recorded weekly, and feces were collected at 0, 4, and 8 weeks. At the age of 9 months, intestinal permeability was assessed by oral gavage of fluorescein isothiocyanate–dextran. Thereafter, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The microarchitecture of the distal femur was assessed by micro-computed tomography and biomechanical properties were evaluated by cyclic reference point indentation. VDD did not affect BMD or most bone microarchitecture parameters, however, the polar moment of inertia (p < 0.05) was higher in the VDD groups compared to vitamin D sufficient groups. VDD mice also had lower whole bone water content (p < 0.05) and a greater average unloading slope (p < 0.01), and energy dissipated (p < 0.01), indicating the femur displayed a brittle phenotype. In addition, VDD caused a greater increase in energy intake (p < 0.05), weight gain (p < 0.05), and a trend for higher intestinal permeability (p = 0.08). The gut microbiota of the VDD group had a reduction in alpha diversity (p < 0.05) and a lower abundance of ASVs from Rikenellaceae, Clostridia_UCG-014, Oscillospiraceae, and Lachnospiraceae (p < 0.01). There was little to no effect of alcohol supplementation on outcomes. Overall, these findings suggest that vitamin D deficiency causes excess weight gain and reduces the biomechanical strength of the femur as indicated by the higher average unloading slope and energy dissipated without an effect on BMD in a mature murine model.

Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota.

The timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM2.5) that impairs offspring's energy metabolism and gut microbiota composition. Unexposed female and male C57BL/6J mice were mated. PM2.5 or filtered air (FA) exposure occurred only in gestation (PM2.5/FA) or lactation (FA/PM2.5). We studied the offspring of both genders. PM2.5 exposure during gestation increased body weight (BW) at birth and from weaning to young in male adulthood. Leptin levels, food intake, Agrp, and Npy levels in the hypothalamus were also increased in young male offspring. Ikbke, Tnf increased in male PM2.5/FA. Males from FA/PM2.5 group were protected from these phenotypes showing higher O2 consumption and Ucp1 in the brown adipose tissue. In female offspring, we did not see changes in BW at weaning. However, adult females from PM2.5/FA displayed higher BW and leptin levels, despite increased energy expenditure and thermogenesis. This group showed a slight increase in food intake. In female offspring from FA/PM2.5, BW, and leptin levels were elevated. This group displayed higher energy expenditure and a mild increase in food intake. To determine if maternal exposure to PM2.5 could affect the offspring's gut microbiota, we analyzed alpha diversity by Shannon and Simpson indexes and beta diversity by the Linear Discriminant Analysis (LDA) in offspring at 30 weeks. Unlike males, exposure during gestation led to higher adiposity and leptin maintenance in female offspring at this age. Gestation exposure was associated with decreased alpha diversity in the gut microbiota in both genders. Our data support that exposure to air pollution during gestation is more harmful to metabolism than exposure during lactation. Male offspring had an unfavorable metabolic phenotype at a young age. However, at an older age, only females kept more adiposity. Ultimately, our data highlight the importance of controlling air pollution, especially during gestation.

Schwann cells contribute to demyelinating diabetic neuropathy and nerve terminal structures in white adipose tissue

Peripheral neuropathy, which can include axonal degeneration and/or demyelination, impacts adipose tissues with obesity, diabetes, and aging. However, the presence of demyelinating neuropathy had not yet been explored in adipose. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), a glial support cell that myelinates axons and contributes to nerve regeneration after injury. We performed a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, and changes across altered energy balance states. We found that mouse scWAT contains both myelinated and unmyelinated nerves and is populated by SCs, including SCs that were associated with synaptic vesicle-containing nerve terminals. BTBR ob/ob mice, a model of diabetic peripheral neuropathy, exhibited small fiber demyelinating neuropathy and alterations in SC marker gene expression in adipose that were similar to obese human adipose. These data indicate that adipose SCs regulate the plasticity of tissue nerves and become dysregulated in diabetes.

The impact of environmental and nutritional stresses on milk fat synthesis in dairy cows

Stress reduces milk and milk components synthesis and increases maintenance requirements of cows. The major stress-related alterations involve enhanced secretion of glucocorticoids and increased sympathetic nervous system activity, which results in biochemical and physiologic changes. In dairy cows exposed to social (ie housing conditions, overstocking, regrouping, feed delivery), physiological (ie initiation of lactation and parturition), or physical (ie heat or cold stress) stressors, responses involve alterations in energy balance and nutrient partitioning. The capacity of the animal to synthesize milk fat largely depends on the availability of substrates for lipid synthesis from the diet, ruminal fermentation or adipose tissue stores, all of which can be altered under stress conditions. Indeed, milk fat concentration is particularly responsive to diet and environment modifications, where a wide range of nutritional and non-nutritional factors influence milk fat output. Milk fat synthesis is an energy demanding process, and extremely sensitive to stress factors during lactation and the involvement of multiple organs. Recent studies examining social, physical, and physiological stressors have provided important insights into how differences in milk yield and milk components may be associated with biological responses to stress factors in dairy cows. This review focuses primarily on the role of stress sources and indicators to which the dairy cow is exposed in regulating milk fat synthesis. We will review the role of nutritional and non-nutritional factors on milk fat synthesis in dairy cows under stress conditions.

Predictors of undernutrition in COPD patients

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by persistent respiratory symptoms and airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report recommends smoking cessation, pharmacological therapy and pulmonary rehabilitation, but this clinical course can be negatively influenced by undernutrition, a condition documented in about 20% of COPD patients. An altered energy balance characterized by an insufficient intake of energy and nutrients is the primary cause of undernutrition, therefore the aim of this study is to investigate whether clinical and instrumental variables collected during a routine respiratory assessment associate with an altered energy balance in order to identify COPD patients at higher risk of undernutrition worth of further assessment. A total of forty-nine participants with a diagnosis of stable COPD were included in this mono-center and longitudinal study. Subjects underwent a multidimensional assessment including evaluation of medical history, evaluation of pulmonary function, evaluation of nutritional status, evaluation of energy intake and resting energy expenditure (REE) using EPIC questionnaire and indirect-calorimetry (IC), respectively, evaluation of physical impairment and mood status. The 24% of participants was at risk of undernutrition with a mean energy intake, total protein intake and lipid intake significantly lower than not at risk subjects, while REE was significantly higher. Age, sex, multimorbidity, disability and depression, and pulmonary function tests were not associated with a negative energy balance, with the exception of the Cumulative Illness Rating Scale (CIRS) severity index, which showed a significant association. Clinical evaluation and pulmonary function tests are unable to reliably predict undernutrition in COPD patients, so a nutritional screening should always be forecast in this population based on an accurate evaluation of energy intake and expenditure and body composition.

1321-P: Reproductive Experience Impairs Warm Sensing in Female Mice

The maternal body experiences drastic alterations in energy balance during pregnancy and lactation, but little is known about the long-term metabolic changes after this reproductive experience. Here we systemically compared the metabolic phenotypes in reproductive experienced (RE) female mice vs. virgin females, and found that RE mice showed a chronic hypothermia when housed at the room temperature (24°C) . In a warm sensing test, virgin females show clear preference to 30 °C ambient temperature vs. the room temperature, while RE mice lose this preference. In a cold sensing test, both virgin and RE females showed similar preference to the room temperature vs. 15 °C ambient temperature. Immunofluorescence staining revealed that expression of estrogen receptor alpha (ERα) in the medial preoptic area (MPA) was significantly decreased in the RE mice compared to virgins. Electrophysiological recordings demonstrated that the warm-sensing property of ERα neurons in the MPA were impaired in RE mice. Our results indicate that reproductive experience impairs the thermoregulation in female mice, associated with defective warm sensing of ERα neurons in the MPA. Disclosure N.Zhang: None. Y.He: None. Y.Xu: None.

Energy Balance and Muscular Power Alterations Following Repeated 4‐Hour Exercise Dives

Divers often perform repeated dives with taxing activity using various underwater breathing apparatuses (UBA), which may increase total energy expenditure (TEE) and alter energy balance (EB) and physical ability. However, data is lacking regarding metabolic and muscular responses to repeated diving. We tested the hypotheses that repeated diving induces negative EB and decreases muscular force, but these decrements would not be affected by UBA. 16 military divers participated in 3 4‐hr dives (31 ± 2 °C) at 1.3 ata, with 20‐hr surface intervals, while wearing a MK25 (n=8, age: 33.8 ± 4.4 yr) UBA with 100% oxygen or MK20 (n=8, age: 36.0 ± 4.7 yr) with air. During dives, subjects alternated 30 min rest and cycling exercise at 60% HRmax. EB was calculated as TEE – energy intake (EI). TEE was measured via doubly labeled water (DLW; 4‐8 atom % 2H2O and 8‐12 atom % 18O). Urine samples were taken before each dive, and for 4 days after diving to assess differences in EB diving and non‐diving (control) days. EI was assessed via food logs. EB, TEE, and EI were normalized to body weight. Before and after each dive, peak force (PF) and rate of power development (RPD) were measured on a force plate during 3 countermovement jumps (3J) and while hopping in place for 10 sec (Hop). EB and muscular power were analyzed with mixed model ANOVAs (UBA: MK25 vs MK20, Diving: Dive Day (DD) vs Control Day (CD), Dive: Pre vs Post Dive, Repeated Diving: Dive 1, 2, 3). There was no effect of UBA on EB during dive days (MK25: ‐12.8 ± 8.9 kcal/kg; MK20: ‐8.4 ± 6.2 kcal/kg); but, EB did increase during diving (p &lt; 0.01, DD: ‐13.0 ± 7.6 kcal/kg; CD: ‐6.7 ± 10.4 kcal/kg). There was no effect of UBA on TEE (p = 0.16, MK25: 37.6 ± 5.6 kcal/kg, MK20: 42.3 ± 2.5 kcal/kg) during dive days; but, TEE (p &lt; 0.01) increased on dive days compared to control (DD: 39.6 ± 5.2 kcal/kg; CD: 31.2 ± 7.0 kcal/kg). There was no effect of UBA or diving on EI. 3J‐RPD (p &lt; 0.01) and Hop‐RPD increased (p &lt; 0.01) with repeated diving (3J‐RPD – D1: 11.7 ± 3.9 kW/s vs. D2: 13.0 ± 4.0 kW/s, p &gt; 0.05; D1 vs. D3: 13.7 ± 3.9 kW/s, p &lt; 0.01; D2 vs. D3, p &gt; 0.05; Hop‐RPD – D1: 37.4 ± 21.6 kW/s vs. D2: 46.1 ± 29.0 kW/s, p = 0.02; D1 vs. D3: 49.9 ± 27.1 kW/s, p &lt; 0.01; D2 vs. D3, p &gt; 0.05). There was a group effect for 3J‐PF (p = 0.02) and 3J‐RPD (p &lt; 0.01) with higher PF (MK25: 1948 ± 205 N; MK20: 1655 ± 223 N) and RPD (MK25: 15.2 ± 3.5 kW/s; MK20: 10.4 ± 2.9 kW/s) in MK25, but no other effects. Repeated 4‐hr exercise dives induce negative EB due to higher TEE, independent of UBA. RPD increased after repeated diving; however, further research is needed to determine mechanisms.

Role of the Autonomic Nervous System in Mechanism of Energy and Glucose Regulation Post Bariatric Surgery.

Even though lifestyle changes are the mainstay approach to address obesity, Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most effective and durable treatments facing this pandemic and its associated metabolic conditions. The traditional classifications of bariatric surgeries labeled them as “restrictive,” “malabsorptive,” or “mixed” types of procedures depending on the anatomical rearrangement of each one of them. This conventional categorization of bariatric surgeries assumed that the “restrictive” procedures induce their weight loss and metabolic effects by reducing gastric content and therefore having a smaller reservoir. Similarly, the “malabsorptive” procedures were thought to induce their main energy homeostatic effects from fecal calorie loss due to intestinal malabsorption. Observational data from human subjects and several studies from rodent models of bariatric surgery showed that neither of those concepts is completely true, at least in explaining the multiple metabolic changes and the alteration in energy balance that those two surgeries induce. Rather, neuro-hormonal mechanisms have been postulated to underly the physiologic effects of those two most performed bariatric procedures. In this review, we go over the role the autonomic nervous system plays- through its parasympathetic and sympathetic branches- in regulating weight balance and glucose homeostasis after SG and RYGB.

Disorders of Puberty in Girls

Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.

Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content

Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese (Ay/a) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in Ay/a mice (Ay/aTg) prevents increased body weight, without reducing food intake. Instead, obesity resistance in Ay/aTg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the Ay/a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring.

The Role of GIP Receptor in the CNS for the Pathogenesis of Obesity.

Glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) is a hormone produced in the upper gut and secreted to the circulation in response to the ingestion of foods, especially fatty foods. Growing evidence supports the physiological and pharmacological relevance of GIP in obesity. In an obesity setting, inhibition of endogenous GIP or its receptor leads to decreased energy intake, increased energy expenditure, or both, eventually causing weight loss. Further, supraphysiological dosing of exogenous long-lasting GIP agonists alters energy balance and has a marked antiobesity effect. This remarkable yet paradoxical antiobesity effect is suggested to occur primarily via the brain. The brain is capable of regulating both energy intake and expenditure and plays a critical role in human obesity. In addition, the GIP receptor is widely distributed throughout the brain, including areas responsible for energy homeostasis. Recent studies have uncovered previously underappreciated roles of the GIP receptor in the brain in the context of obesity. This article highlights how the GIP receptor expressed by the brain impacts obesity-related pathogenesis.