Long-term Body Weight Gain Research Articles

Lower hypothalamus subunit volumes link with impaired long-term body weight gain after preterm birth.

Preterm birth is associated with an increased risk for impaired body weight gain. While it is known that in prematurity several somatic and environmental factors (e.g., endocrine factors, nutrition) modulate short- and long-term body weight gain, the contribution of potentially impaired body weight control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in body weight control is altered after preterm birth, with these alterations being associated with aberrant body weight development into adulthood. We assessed 101 very preterm (i.e., <32 weeks of gestational age) and/or very low birth weight (i.e., <1500g; VP/VLBW) and 110 full-term born (FT) adults of the population-based Bavarian Longitudinal Study with T1-weighted MRI, deep learning-based hypothalamus subunit segmentation, and multiple body weight assessments from birth into adulthood. Volumes of the whole hypothalamus and hypothalamus subunits relevant for body weight control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and body weight trajectories (i.e., trajectory slopes and cluster/types such as long-term catch-up growth). Particularly, VP/VLBW subgroups, whose individuals showed catch-up growth and/or were small for gestational age, were mostly associated with volumes of distinct hypothalamus subunits such as lateral or infundibular/ventromedial hypothalamus. Results demonstrate lower volumes of body weight control-related hypothalamus subunits after preterm birth that link with long-term body weight gain. Data suggest postnatal development of body weight -related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body weight trajectories into adulthood.

Chronic social stress lessens the metabolic effects induced by a high-fat diet.

Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high-fat diet (HFD), aggravates the metabolic phenotype and whether there are particularly sensitive time windows for the negative consequences of HFD exposure. Chronically stressed male mice and controls (CTRL) were kept under (i) SD-conditions, (ii) with HFD commencing post-CSD, or (iii) provided with HFD lasting throughout and after CSD. Under SD conditions, stress increased glucose levels early post-CSD. Both HFD regimens increased glucose levels in non-stressed mice but not in stressed mice. Nonetheless, when HFD was provided after CSD, stressed mice did not differ from controls in long-term body weight gain, fat tissue mass and plasma insulin, and leptin levels. In contrast, when HFD was continuously available, stressed mice displayed reduced body weight gain, lowered plasma levels of insulin and leptin, and reduced white adipose tissue weights as compared to their HFD-treated non-stressed controls. Interestingly, stress-induced adrenal hyperplasia and hypercortisolemia were observed in mice treated with SD and with HFD after CSD but not in stressed mice exposed to a continuous HFD treatment. The present work demonstrates that CSD can reduce HFD-induced metabolic dysregulation. Hence, HFD during stress may act beneficially, as comfort food, by decreasing stress-induced metabolic demands.

Tracking human fat turnover with carbon dating

Lipid turnover in adipose tissue is important in long-term body weight gain and weight loss maintenance after bariatric surgery in humans.

Regulation of energy expenditure and substrate oxidation by short-chain fatty acids.

Short-chain fatty acids (SCFAs) are metabolites produced from the fermentation of dietary fibre by the gut microbiota. High-fibre diets have been associated with lower weight gain and a number of reports have therefore investigated if these positive effects of a dietary fibre on body weight can be replicated through the direct administration of SCFAs. Many of these studies have reported that SCFAs can prevent or attenuate long-term body weight gain by increasing energy expenditure through increased lipid oxidation. The aim of the present review is to therefore evaluate the current evidence for an effect of SCFAs on whole-body energy expenditure and to assess the potential underlying mechanisms. The available data highlights that SCFAs can exert multiple effects at various organ and tissue sites that would cumulatively raise energy expenditure via a promotion of lipid oxidation. In conclusion, the present review proposes that dietary interventions and other therapies that augment gut-derived SCFAs and systemic availability may present an effective strategy to improve long-term energy balance and body weight management.

Long-term Body Weight Gain After Maturity is Associated With the Incidence of Chronic Kidney Disease (CKD), Independent of Current Body Weight, in Middle-aged and Older Men.

BackgroundThis study investigated the relationship between long-term body weight gain after maturity and the incidence of chronic kidney disease (CKD).MethodsThe participants were 303 men without a history of cardiovascular and cerebrovascular diseases, kidney dysfunction, or dialysis treatment. Their body weight gain after maturity was examined using a standardized self-administered questionnaire. The participants were divided into two groups based on the presence/absence of a body weight gain of ≥10 kg since 20 years of age.ResultsAfter a 6-year follow-up, the cumulative incidence of CKD was significantly higher in participants with a body weight gain of ≥10 kg than in participants without body weight a body weight gain of ≥10 kg since 20 years of age (log-rank test: P = 0.041). After adjusting for the age, body mass index, estimated glomerular filtration rate levels, smoking and drinking habits, and the presence of hypertension, dyslipidemia, and hyperglycemia at baseline, the normal body weight participants with a body weight gain of ≥10 kg since 20 years of age was significantly related to the incidence of CKD (hazard ratio 2.47; 95% confidence of interval, 1.02–6.01, P = 0.045).ConclusionsThese results suggest that long-term body weight gain after maturity in normal body weight participants may be associated with the incidence of CKD, independent of current body weight.

Maternal Choline Intake Programs Hypothalamic Energy Regulatory Pathways and Long-Term Phenotype in Male Wistar Rat Offspring (OR35-04-19)

ObjectivesThe prenatal period is a critical time of brain development. Maternal choline intake is associated with improvement in memory and cognitive function in the offspring. However, the role of choline in the regulation of physiological functions controlled by the hypothalamus has not been reported. The objective of this study is to elucidate the effects of choline intake on the in utero programming of hypothalamic energy regulatory neurons in male Wistar rat offspring. MethodsPregnant Wistar rats received an AIN-93G diet containing recommended choline (RC, 1 g/kg diet), low choline (LC, 0.5-fold), or high choline (HC, 2.5-fold). At birth, brain and blood was collected from male pups. Male pups from each dietary treatment were maintained on the control diet for 17-weeks. Dependent measures include post-weaning food intake, energy expenditure, weight-gain, plasma glucoregulatory hormones, brain choline and 1-carbon metabolite levels, and expression of hypothalamic energy regulatory neurons. ResultsAt birth, pup brain concentrations of choline proportionally reflected the choline content in the maternal diets. HC pups had higher hypothalamic protein expression of the orexigenic neuropeptide-Y neuron than both groups (P < 0.05), but lower activation than LC pups (P < 0.05). Both HC and LC pups had lower plasma leptin concentrations than RC pups (P < 0.01), but LC pups had lower hypothalamic leptin receptor expression compared to both groups at birth (P < 0.05). During adulthood, offspring of HC dams had higher weekly food intake compared to RC (11%, P < 0.01), and higher weight-gain than both RC and LC groups (12%, P < 0.05). LC offspring had lower 24hr energy expenditure and locomotor activity than HC and RC groups (6%, P < 0.05). ConclusionsCholine content of diets consumed by rats during pregnancy impacts in utero development of hypothalamic energy regulatory systems; long-term body weight-gain, food intake and energy expenditure in mature rat offspring. Funding SourcesThis research was supported by the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD).

Excess Folic Acid Supplementation Before and During Pregnancy and Lactation Activates Fos Gene Expression and Alters Behaviors in Male Mouse Offspring.

Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects and other birth defects. After 20 years mandate food fortification with FA, serum concentration of folate and unmetabolized FA increased significantly in the North American population. But whether excess FA intake impairs neurodevelopment and behavior is still controversial. Here, we treated mice with approximately 2.5-fold (moderate dose of FA, MFA) or 10-fold (high dose of FA, HFA) the dietary requirement of FA 1 week before mating and throughout pregnancy and lactation, and examined behaviors in adult male offspring using open field test, three-chamber sociability and social novelty test, elevated plus maze, rotarod and Morris water maze. We found that early life MFA supplementation increased long-term body weight gain in adults, elevated anxiety-like behavior, and impaired social preference, motor learning and spatial learning ability without modifying motor ability and spatial memory. In contrast, HFA supplementation only induced mild behavioral abnormality. RNA sequencing revealed that FA supplementation altered the expression of brain genes at weaning, among which Fos and related genes were significantly up-regulated in MFA mice compared with control and HFA mice. Quantitative real time-PCR (qRT-PCR) and western blots confirmed the increase of these genes. Our results suggested that FA supplementation during early life stage affected gene expression in weaning mice, and exhibited long-term impairments in adult behaviors in a dose-sensitive manner.

Repeated neonatal propofol administration induces sex-dependent long-term impairments on spatial and recognition memory in rats.

Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner.

Long‐term human growth hormone expression and partial phenotypic correction by plasmid‐based gene therapy in an animal model of isolated growth hormone deficiency

A model for in vivo gene therapy based on electroporation of human growth hormone (hGH)-coding naked DNA in the muscle of dwarf (lit/lit) and immunodeficient dwarf (lit/scid) mice is described. A plasmid containing the ubiquitin C promoter and the genomic hGH sequence was administered to the exposed quadriceps muscle, followed by electrotransfer using eight 50-V pulses of 20 ms at a 0.5-s interval. Serum hGH levels were determined after various days of DNA administration and a long-term body weight gain experiment was carried out. Serum hGH, determined 3 days after DNA administration, revealed a significant dose-response curve (p < 0.01) in the 0-50 microg range. Because 50 microg of plasmid DNA produced circulating hGH levels of 2-3 ng/ml for at least 12 days, a long-term body weight gain assay was carried out. After 60 days, the weight of treated lit/scid mice increased 33.1% compared to a 4.2% weight decrease for the control group. hGH circulating levels were of the order of 1.5-3 ng/ml throughout the experiment and the average weight increase during the first 10 days was comparable to that obtained upon regular daily injection of 10 microg of recombinant hGH per mouse, producing comparable circulating levels of the hormone. A lower, but still significant increase in body weight was obtained upon repeating the experiment in immunocompetent dwarf mice (lit/lit). We report for the first time sustained levels of circulating hGH after intramuscular naked DNA administration and, consequently, a highly significant weight increase of dwarf 'little' mice.

Observational Study of the Impact of Short-Term Duloxetine Treatment on Body Weight in Patients With Major Depressive Disorder

To the Editor: The impact of antidepressants on body weight interferes with patients’ adherence to these medications. In the past, tricyclic antidepressants were associated with weight gain.1 In recent years, even with advances, antidepressants have still struggled solving this complex issue. Selective serotonin reuptake inhibitors (SSRIs) can cause short-term body weight loss, but long-term body weight gain can be a significant concern in this treatment strategy.2 Serotonin-norepinephrine reuptake inhibitor (SNRI) agents, such as venlafaxine and sibutramine, have different effects on body weight. Sibutramine is approved by the US Food and Drug Administration (FDA) for obesity treatment,3 but the effect of venlafaxine on body weight is still controversial.

Effects of neonatal treatment with Tyr-MIF-1 and naloxone on the long-term body weight gain induced by repeated postnatal stressful stimuli

Stressful stimuli repeatedly applied during the first postnatal weeks can induce body weight gain in the mouse during adulthood. This effect can be prevented by injecting naloxone concomitantly with stress. The peptides belonging to the Tyr-MIF-1 family have a great modulating activity on numerous stress-induced phenomena. The aim of the present work was to compare the effect of repeated neonatal injections of Tyr-MIF-1 or naloxone on the long-term body weight gain induced by a stressing procedure applied daily during the first three weeks of life. The results indicate that although naloxone blocked the development of the stress-induced effects, Tyr-MIF-1 potentiated them.