Prevention Of Diet-induced Obesity Research Articles

Front Cover: Whole Agrocybe cylindracea Prevented Obesity Linking with Modification of Gut Microbiota and Associated Fecal Metabolites in High‐Fat Diet‐Fed Mice

Mol. Nutr. Food Res. 2022, 66, 202100897 DOI: 10.1002/mnfr.202100897 Dietary Agrocybe cylindracea (AC) can beneficially modulate the gut microbiota and associated metabolites in HFD-fed mice. The beneficial effects of AC have been identified to significantly correlate with its prevention of diet-induced obesity and its complications. This is reported by Yu Ding and co-workers in article number 2100897.

Dietary Supplementation with Dunaliella Tertiolecta Prevents Whitening of Brown Fat and Controls Diet-Induced Obesity at Thermoneutrality in Mice.

We investigated the effect of evodiamine-containing microalga Dunaliella tertiolecta (DT) on the prevention of diet-induced obesity in a thermoneutral C57BL/6J male (30 °C). It attenuates the activity of brown adipose tissue (BAT), which accelerates diet-induced obesity. Nine-week-old mice were fed a high-fat diet supplemented with 10 g (Low group) or 25 g (High group) DT powder per kg food for 12 weeks. Compared to control mice without DT supplementation, body weight gain was significantly reduced in the High group with no difference in food intake. Tissue analyses indicated maintenance of multilocular morphology in BAT and reduced fat deposition in liver in DT-supplemented mice. Molecular analysis showed a significant decrease in mammalian target of rapamycin−ribosomal S6 protein kinase signaling pathway in white adipose tissue and upregulation in mRNA expression of brown fat-associated genes including fibroblast growth factor-21 (Fgf21) and uncoupling protein 1 (Ucp1) in BAT in the High group compared to the control. In the experiments using C3H10T1/2 adipocytes, DT extract upregulated mRNA expression of brown fat-associated genes in dose-dependent and time-dependent manners, accompanied by a significant increase in secreted FGF21 levels. Our data show the ability of DT as a nutraceutical to prevent brown fat attenuation and diet-induced obesity in vivo.

Early life stress reduces voluntary exercise and its prevention of diet-induced obesity and metabolic dysfunction in mice.

The development of obesity-related metabolic syndrome (MetS) involves a complex interaction of genetic and environmental factors. One environmental factor found to be significantly associated with MetS is early life stress (ELS). We have previously reported on our mouse model of ELS, induced by neonatal maternal separation (NMS), that displays altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased sensitivity in the urogenital organs, which was attenuated by voluntary wheel running. Here, we are using our NMS model to determine if ELS-induced changes in the HPA axis also influence weight gain and MetS. Naïve (non-stressed) and NMS male mice were given free access to a running wheel and a low-fat control diet at 4-weeks of age. At 16-weeks of age, half of the mice were transitioned to a high fat/sucrose (HFS) diet to investigate if NMS influences the effectiveness of voluntary exercise to prevent diet-induced obesity and MetS. Overall, we observed a greater impact of voluntary exercise on prevention of HFS diet-induced outcomes in naïve mice, compared to NMS mice. Although body weight and fat mass were still significantly higher, exercise attenuated fasting insulin levels and mRNA levels of inflammatory markers in epididymal adipose tissue in HFS diet-fed naïve mice. Only moderate changes were observed in exercised NMS mice on a HFS diet, although this could partially be explained by reduced running distance within this group. Interestingly, sedentary NMS mice on a control diet displayed impaired glucose homeostasis and moderately increased pro-inflammatory mRNA levels in epididymal adipose, suggesting that early life stress alone impairs metabolic function and negatively impacts the therapeutic effect of voluntary exercise.

Artemisia sphaerocephala Krasch polysaccharide mediates lipid metabolism and metabolic endotoxaemia in associated with the modulation of gut microbiota in diet-induced obese mice

Artemisia sphaerocephala Krasch polysaccharide (ASKP) has been proved to have many bioactivities. To determine the underlying mechanisms on anti-obesogenic effect of ASKP in mice, parameters related to obesity, gut microbiota composition, and the correlation between the parameters and specific bacterial taxa were investigated. The results showed that ASKP significantly alleviated high-fat-diet-induced obesity in mice with the amelioration of dyslipidemia, and metabolic endotoxaemia. Relative expression analyses of genes indicated that ASKP administration modulated hepatic lipid metabolism with the downregulation of related genes, including ACC-1, FAS, SREBP-1c, and PPARγ. 16S rRNA analysis showed that ASKP mediated the gut dysbiosis induced by high-fat diet, such as the reduction of Proteobacteria, AF12, and Helicobacter. Spearman’s correlation showed that some specific genera, such as Odoribacter, AF12, and Rikenella, were strongly associated with obesity-related parameters. Our results demonstrated that ASKP could serve as a potential prebiotic agent in the prevention of diet-induced obesity.

Specific knockout of p85α in brown adipose tissue induces resistance to high-fat diet–induced obesity and its metabolic complications in male mice

ObjectiveAn increase in mass and/or brown adipose tissue (BAT) functionality leads to an increase in energy expenditure, which may be beneficial for the prevention and treatment of obesity. Moreover, distinct class I PI3K isoforms can participate in metabolic control as well as in systemic dysfunctions associated with obesity. In this regard, we analyzed in vivo whether the lack of p85α in BAT (BATp85αKO) could modulate the activity and insulin signaling of this tissue, thereby improving diet-induced obesity and its associated metabolic complications. MethodsWe generated BATp85αKO mice using Cre-LoxP technology, specifically deleting p85α in a conditional manner. To characterize this new mouse model, we used mice of 6 and 12 months of age. In addition, BATp85αKO mice were submitted to a high-fat diet (HFD) to challenge BAT functionality. ResultsOur results suggest that the loss of p85α in BAT improves its thermogenic functionality, high-fat diet–induced adiposity and body weight, insulin resistance, and liver steatosis. The potential mechanisms involved in the improvement of obesity include (1) increased insulin signaling and lower activation of JNK in BAT, (2) enhanced insulin receptor isoform B (IRB) expression and association with IRS-1 in BAT, (3) lower production of proinflammatory cytokines by the adipose organ, (4) increased iWAT browning, and (5) improved liver steatosis. ConclusionsOur results provide new mechanisms involved in the resistance to obesity development, supporting the hypothesis that the gain of BAT activity induced by the lack of p85α has a direct impact on the prevention of diet-induced obesity and its associated metabolic complications.

The Effects of Pasteurization Types on the Content and Isomerization of Conjugated Linoleic Acid in Milk

The world is currently facing an epidemic of giant proportions – diet‐induced obesity (DIO) and associated co‐morbidities (type 2 diabetes, hypertension, certain cancers, etc.). While diet and exercise are the gold standards for treatment and prevention of DIO, isomers of conjugated linoleic acid (CLA) (cis‐9/trans‐11 and trans‐10/cis‐12) have been shown to reduce body fat mass and increase lean tissue mass, and more importantly, aid in the treatment of a host of co‐morbidities. Apart from supplementation, meat and dairy products from ruminants (cows, sheep, and goats) are the major source of CLA for humans. However, CLA composition ranges greatly in these products as processing i.e. cooking, pasteurization, etc. alters the content of CLA as well the isomers themselves. As the extend of these changes are unknown, the effects of time and temperature on CLA isomerization in milk through varying pasteurization types was investigated. First, raw milk samples were obtained from a local farm, and subjected to three different types of pasteurization – vat, ultra, and high temperature, short time pasteurization. Results show that the ultra‐high temperature pasteurized sample had more trans/trans isomerization than the raw sample, while the other samples were comparable to the raw. Therefore, as temperature increased, the extent of CLA isomerization also increased. Further experiments using thermochemistry and kinetics should be conducted to identify the times and temperatures at which each isomer is converted or formed. This knowledge could then be used to produce more beneficial CLA within a given sample and to decrease the undesired trans/trans CLA.Support or Funding InformationSupport for this work was provided by the Department of Chemistry, Maryville College.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Prevention of diet-induced obesity in rats by oral application of collagen fragments

The aim of the present study was to determine whether orally applied collagen fragments (CFs) could affect the development of obesity in obese rats. To this end, experimental rats that were exposed to a high-calorie diet (HCD) for four weeks were randomly divided into two groups: HCD and HCD+CFs, with both groups continuing to receive the HCD. However, rats from the HCD+CFs group were also provided with CFs in a 0.05-M citrate buffer (pH 5.0) (1 g·kg -1 of body weight) by intragastric administration, every other day for the next six weeks. Selected parameters associated with obesity development and insulin resistance, as well as serum markers of oxidative stress and the cytokine profile were assessed at the end of the 10 th week. Supplementation with CFs resulted in a decrease in body weight and body mass index when compared to animals exposed to a HCD. The observed changes were assumed to be caused by a lower food intake and increased water intake by obese rats treated with CFs. Enhanced activity of superoxide dismutase (SOD), catalase (CAT) and decreased malondialdehyde (MDA) concentration were detected in the HCD+CF group of animals when compared to untreated HCD-fed rats. Administration of CFs also lowered the serum concentrations of the proinflammatory cytokines IL-1β and IL-12, whereas the concentration of the anti-inflammatory cytokine IL-10 was significantly increased and the concentration of cytokine IL-4 was near the control value. Decreased concentrations of fasting blood glucose, glycated hemoglobin (GHbA1c) and serum insulin and increased tolerance to glucose in the oral glucose tolerance test (OGTT) were observed in the HCD+CF group of animals when compared to rats in the HCD group. We concluded that CFs mediated a therapeutic effect on obesity development in rats exposed to a HCD by affecting pathways involved in obesity pathogenesis. https://doi.org/10.2298/ABS170401027R Received: April 1, 2017; Revised: June 1, 2017; Accepted: June 13, 2017; Published online: August 1, 2017 How to cite this article: Raksha NG, Potalitsyn PY, Yurchenko AV, Halenova TI, Savchuk OM, Ostapchenko LI. Prevention of diet-induced obesity in rats by oral application of collagen fragments. Arch Biol Sci. 2018;70(1):77-86.

Hop Phytochemicals and Their Potential Role in Metabolic Syndrome Prevention and Therapy.

Historically, hop cones (Humulus lupulus) have been used since ancient times as a remedy for many ailments and, as a source of polyphenols and bitter acids, is very effective in the treatment of metabolic syndrome (MS). Hop flavonoids, particularly xanthohumol (XN), are substances with hypoglycemic, antihyperlipidemic, and antiobesity activities. Iso-α-acids (IAA) and matured hop bitter acids (MHBA) improve health by influencing lipid metabolism, glucose tolerance, and body weight. The modulatory effect of IAA and MHBA on lipid metabolism may also be responsible for a loss in body weight. These results suggest promising applications for IAA, MHBA, and XN in humans, particularly in the prevention of diet-induced obesity and diabetes.

Abstract 1258: Lifestyle improvements delay cancer onset and progression by adapting endocrine and immune signaling in mouse models

Abstract Metabolic syndromes instigate substantial morbidity and mortality worldwide via its negative effects of many diseases including cancer. Obesity in particular has been deemed a causative factor for breast cancer in post-menopausal women, while worsening prognosis regardless of menopausal status. Importantly, progression of many metabolic syndromes can largely be slowed or reversed with aggressive lifestyle changes, thus also having the potential to mitigate cancer onset. A mouse model of environmental enrichment (EE) to improve motosensory, cognitive, and social stimulation by increasing physical engagement and social interaction triggers vast improvements in overall health. These include boosting mental health, reducing adiposity, prevention of diet-induced obesity (DIO), promoting the white to brown fat transition, enhancing insulin sensitivity, improving immune function, limiting inflammation, and inhibition of cancer growth. We have elucidated the central mechanism of EE to be the activation of the hypothalamic-sympathoneural-adipocyte (HSA) axis, a specific neuroendocrine route in which the brain communicates with adipose tissue via the sympathetic nervous system. Once activated, norepinephrine (NE) is released directly onto adipose tissue which induces the observed metabolic improvements. Breast cancer is uniquely exposed to this adipose-NE so we sought to explore this distinctive microenvironment in the context of both local and systemic endocrine and immune signaling in varied body mass states and menopausal statuses. Our data showed that EE diminished leptin levels and delayed cancer onset in the MMTV-PyMT spontaneous mouse model of breast cancer and slowed growth in a DIO allograft model. In contrast, EE failed to attenuate tumor progression in ob/ob mice in the absence of leptin, but rather enhanced tumor growth, suggesting that the leptin-NE relationship is one of the key peripheral mediators of the EE anti-breast cancer effects. We also observed significant immune cell modulation in the adipose tissue following EE. Initial characterization revealed a decrease in the proportion of tumor-associated macrophages (TAMs) and an overall anti-inflammatory response which together with the drop in leptin may contribute to the observed anti-cancer effects. We plan to further elucidate this EE-induced adipose and immune cell modulation with the ultimate goal of developing therapeutic strategies to treat both metabolic syndromes as well as associated and possibly independent cancer types. Citation Format: Grant D. Foglesong, Stephen M. Bergin, Wei Huang, Michael A. Caligiuri, Lei Cao. Lifestyle improvements delay cancer onset and progression by adapting endocrine and immune signaling in mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1258. doi:10.1158/1538-7445.AM2017-1258

Beyond the Role of Dietary Protein and Amino Acids in the Prevention of Diet-Induced Obesity

High-protein diets have been shown to prevent the development of diet-induced obesity and can improve associated metabolic disorders in mice. Dietary leucine supplementation can partially mimic this effect. However, the molecular mechanisms triggering these preventive effects remain to be satisfactorily explained. Here we review studies showing a connection between high protein or total amino nitrogen intake and obligatory water intake. High amino nitrogen intake may possibly lower lipid storage, and prevent insulin resistance. Suggestions are made for further systematical studies to explore the relationship between water consumption, satiety, and energy expenditure. Moreover, these examinations should better distinguish between leucine-specific and unspecific effects. Research in this field can provide important information to justify dietary recommendations and strategies in promoting long-term weight loss and may help to reduce health problems associated with the comorbidities of obesity.

Prevention of diet-induced obesity in C57BL/BJ mice with addition of 2 % dietary green tea but not with cocoa or coffee to a high-fat diet

Prevention of diet-induced obesity in C57BL/BJ mice with addition of 2 % dietary green tea but not with cocoa or coffee to a high-fat diet

Prevention of diet-induced obesity in C57BL/BJ mice with addition of 2 % dietary green tea but not with cocoa or coffee to a high-fat diet

Most of the fat oxidation effects of green tea have been observed in a beverage form. This study explored the use of green tea as feed formation in obese mice to protect against diet-induced obesity. Forty-eight adult C57BL/6J mice were randomised to either a control diet with 36.1 % w/w sucrose or a standard diet, except for the replacement of 2 % w/w of the sucrose dietary component (36.1 % sucrose in control) with 2 % w/w cocoa (34.1 % sucrose), 2 % w/w coffee, or 2 % w/w powdered Japanese green tea. At 16th week, body composition, plasma glucose, organ samples and bone mineral density were obtained. In comparison to the control group, only the 2 % green tea group displayed lower body weight (p < 0.01), body fat, liver weight (p < 0.05), hepatic lipid status and higher lean mass. The coffee group displayed lower body fat (p < 0.05) and the cocoa group lower plasma glucose (p < 0.05), but this was not substantiated by other parameters. Results of study indicate the anti-obesity potential of green tea when consumed as 2 % (w/w %) of the diet probably by lipolysis and decreased systemic inflammation resulting from consumption of a high-fat, high-sucrose diet in obesity-prone strain of mice.

Glucose Transporter-8 (GLUT8) Mediates Glucose Intolerance and Dyslipidemia in High-Fructose Diet-Fed Male Mice

Members of the glucose transporter (GLUT) family of membrane-spanning hexose transporters are subjects of intensive investigation for their potential as modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2 diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed class III dual-specificity glucose and fructose transporter, GLUT8, has important metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8 mediates the deleterious metabolic effects of chronic high-fructose diet exposure. Here we demonstrate resistance to high-fructose diet-induced glucose intolerance and dyslipidemia concomitant with enhanced oxygen consumption and thermogenesis in GLUT8-deficient male mice. Independent of diet, significantly lower systolic blood pressure both at baseline and after high-fructose diet feeding was also observed by tail-cuff plethysmography in GLUT8-deficient mice vs wild-type controls. Resistance to fructose-induced metabolic dysregulation occurred in the context of enhanced hepatic peroxisome proliferator antigen receptor-γ (PPARγ) protein abundance, whereas in vivo hepatic adenoviral GLUT8 overexpression suppressed hepatic PPARγ expression. Taken together, these findings suggest that GLUT8 blockade prevents fructose-induced metabolic dysregulation, potentially by enhancing hepatic fatty acid metabolism through PPARγ and its downstream targets. We thus establish GLUT8 as a promising target in the prevention of diet-induced obesity, metabolic syndrome, and type 2 diabetes mellitus in males.

Prevention of diet‐induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns

This study was conducted to determine the mechanisms implicated in the beneficial effects of apple polyphenols (APs) against diet-induced obesity in Wistar rats, described in a previous study from our group. Supplementation of high-fat sucrose diet with AP prevented adiposity increase by inhibition of adipocyte hypertrophy. Rats supplemented with AP exhibited improved glucose tolerance while adipocytes isolated from these rats showed an enhanced lipolytic response to isoproterenol. AP intake led to reduced Lep, Plin, and sterol regulatory element binding transcription factor 1 (Srebf1) mRNA levels and increased aquaporin 7 (Aqp7), adipocyte enhancer binding protein 1 (Aebp1), and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (Ppargc1a) mRNA levels in epididymal adipocytes. In addition, we found different methylation patterns of Aqp7, Lep, Ppargc1a, and Srebf1 promoters in adipocytes from apple-supplemented rats compared to high-fat sucrose fed rats. The administration of AP protects against body weight gain and fat deposition and improves glucose tolerance in rats. We propose that AP exerts the antiobesity effects through the regulation of genes involved in adipogenesis, lipolysis, and fatty acid oxidation, in a process that could be mediated in part by epigenetic mechanisms.

Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases

Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-release channel. As a consequence, resveratrol increases NAD+ and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice.

Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance

In obesity, anorectic responses to leptin are diminished, giving rise to the concept of "leptin resistance." Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high-fat-diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity.

Role of Peroxisome Proliferator-activated Receptor δ/β in Hepatic Metabolic Regulation

Pharmacological activation of peroxisome proliferator-activated receptor δ/β (PPARδ/β) improves glucose handling and insulin sensitivity. The target tissues of drug actions remain unclear. We demonstrate here that adenovirus-mediated liver-restricted PPARδ activation reduces fasting glucose levels in chow- and high fat-fed mice. This effect is accompanied by hepatic glycogen and lipid deposition as well as up-regulation of glucose utilization and de novo lipogenesis pathways. Promoter analyses indicate that PPARδ regulates hepatic metabolic programs through both direct and indirect transcriptional mechanisms partly mediated by its co-activator, PPARγ co-activator-1β. Assessment of the lipid composition reveals that PPARδ increases the production of monounsaturated fatty acids, which are PPAR activators, and reduces that of saturated FAs. Despite the increased lipid accumulation, adeno-PPARδ-infected livers exhibit less damage and show a reduction in JNK stress signaling, suggesting that PPARδ-regulated lipogenic program may protect against lipotoxicity. The altered substrate utilization by PPARδ also results in a secondary effect on AMP-activated protein kinase activation, which likely contributes to the glucose-lowering activity. Collectively, our data suggest that PPARδ controls hepatic energy substrate homeostasis by coordinated regulation of glucose and fatty acid metabolism, which provide a molecular basis for developing PPARδ agonists to manage hyperglycemia and insulin resistance.

Prevention of diet-induced obesity by dietary black tea polyphenols extract in vitro and in vivo

Objective The effects of certain tea components on the prevention of obesity in humans have recently been reported, although it is still unclear whether black tea consumption is beneficial. We obtained black tea extract (BTPE) consisting of polyphenols specific to black tea, and from it, prepared a polymerized polyphenol fraction (BTP). The effectiveness of oral administration of the BTPE was examined in in vitro and in vivo experiments. Methods Effects of BTPE or BTP on pancreatic lipase activity were investigated in vitro. Male Wistar rats were administered an oral lipid emulsion containing BTPE at a concentration of 500 or 1000 mg/kg body weight and sequential plasma lipid levels were measured. Female C57BL/6N mice were fed a standard or high-fat diet supplemented with 1% or 5% (w/w) BTPE for 8 wk and changes in body weight were examined. Results BTP and BTPE inhibited pancreatic lipase activity with an IC 50 of 15.5 and 36.4 μg/mL in vitro, respectively. BTPE suppressed increases in rat plasma triglyceride levels in a dose-dependent manner after oral administration of a lipid emulsion. Furthermore, administration of the 5% BTPE suppressed increases in body weight ( P < 0.05), parametrial adipose tissue mass, and liver lipid content (reduced to 56.9% and 81.7% of control mice, respectively, P < 0.05) in mice fed a high-fat diet. Conclusion The BTPE may prevent diet-induced obesity by inhibiting intestinal lipid absorption. It was suggested that the major active component in the BTPE was BTP.

Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype?

LPL is an enzyme involved in the breakdown and uptake of lipoprotein triglycerides. In the present study, we examined how the transgenic (Tg) overexpression of human LPL in mouse skeletal muscle affected tolerance to cold temperatures, cold-induced thermogenesis, and fuel utilization during this response. Tg mice and their nontransgenic controls were placed in an environmental chamber and housed in metabolic chambers that monitored oxygen consumption and carbon dioxide production with calorimetry. When exposed to 4 degrees C, an attenuation in the decline in body temperature in Tg mice was accompanied by an increased metabolic rate (15%; P < 0.001) and a reduction in respiratory quotient (P < 0.05). Activity levels, the expression of uncoupling proteins in brown fat and muscle, and lean mass failed to explain the enhanced cold tolerance and thermogenesis in Tg mice. The more oxidative type IIa fibers were favored over the more glycolytic type IIb fibers (P < 0.001) in the gastrocnemius and quadriceps muscles of Tg mice. These data suggest that Tg overexpression of LPL in skeletal muscle increases cold tolerance by enhancing the capacity for fat oxidation, producing an avian-like phenotype in which skeletal muscle contributes significantly to the thermogenic response to cold temperatures.

Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg.kg(-1).day(-1)) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.