Effect of a high or low ambient perinatal temperature on adult obesity in Osborne-Mendel and S5B/Pl rats (original) (raw)
Related papers
2019
Background and aim: Rodents are commonly housed below thermoneutrality and this exposure to cold (i.e. 20°C) activates thermogenic brown (BAT) and beiging of white adipose tissue. Here, we examined whether a standard housing temperature (i.e. 20°C, a reduction in temperature of ~8°C) or YM-178, a highly-selective β-adrenoreceptor agonist, in obese animals raised at thermoneutrality, would impact differently on classical BAT or subcutaneous inguinal (IWAT) beige depots. Methods: Eighteen weanling Sprague-Dawley rats were housed at thermoneutrality (28°C) and fed a high-fat diet. At 12 weeks, 6 animals were randomised to either standard housing temperature (20°C, n=6) or to β3-AR agonist administration (28°C+β, 0.75mg/kg/d, n=6) for 4 weeks. Metabolic assessment was undertaken during the final 48h, followed by interscapular, perivascular BAT and IWAT sampling for the analysis of thermogenic genes and the proteome. Results: Exposure to 20°C increased weight gain, BAT and IWAT mass. Pro...
Endocrinology, 2007
Excess weight gain during the early postnatal period increases the risk of persistent obesity into adulthood and impacts on the subsequent risk for metabolic and cardiovascular diseases. The current study investigated the long-term effect of early excess weight gain, through reduced nursing litter size, on body weight regulation and its relation to brown adipose tissue (BAT) thermogenesis. Animals raised in a small litter (SL, three pups per litter) were compared with those raised in a normal litter size (NL, eight pups per litter). BAT from young adult NL and SL rats, maintained under either ambient or cold conditions, were used for gene expression, morphological, and functional analysis. Compared with NL, SL rats showed excess weight gain, and adult SL animals had a reduced thermogenic capacity as displayed by lower levels of uncoupling protein 1 (UCP1). When exposed to cold, BAT from SL rats was less active and demonstrated reduced responsiveness to cold. Furthermore, reduction in transcript abundance of several lipid lipases and transcriptional regulators was observed in SL rats either at ambient temperature or under cold conditions. Finally, the expression of sympathetic 3-adrenergic receptor and the response to the sympathetic receptor agonist isoproterenol were decreased in SL rats. Overall, these observations provide the first evidence that postnatal excess weight gain results in abnormalities in BAT thermogenesis and sympathetic outflow, which likely increases susceptibility to obesity in adulthood. (Endocrinology 148: 4150 -4159, 2007)
Frontiers in Physiology
Aim: To investigate whether housing temperature influences rat adiposity, and the extent it is modified by diet and/or pregnancy. Housing temperature impacts on brown adipose tissue, that possess a unique uncoupling protein (UCP) 1, which, when activated by reduced ambient temperature, enables rapid heat generation. Methods: We, therefore, examined whether the effects of dietary induced rise in fat mass on interscapular brown fat in female rats were dependent on housing temperature, and whether pregnancy further modulates the response. Four week old rats were either maintained at thermoneutrality (27 • C) or at a "standard" cool temperature (20 • C), and fed either a control or obesogenic (high in fat and sugar) diet until 10 weeks old. They were then either tissue sampled or mated with a male maintained under the same conditions. The remaining dams were tissue sampled at either 10 or 19 days gestation. Results: Diet had the greatest effect on fat mass at thermoneutrality although, by 19 days gestation, fat weight was similar between groups. Prior to mating, the abundance of UCP1 was higher at 20 • C, but was similar between groups during pregnancy. UCP1 mRNA followed a similar pattern, with expression declining to a greater extent in the animals maintained at 20 • C. Conclusion: Housing temperature has a marked influence on the effect of dietary induced rise in fat deposition that was modified through gestation. This maybe mediated by the reduction in UCP1 with housing at thermoneutrality prior to pregnancy and could subsequently impact on growth and development of the offspring.
β-Adrenergic Receptors, Diet-induced Thermogenesis, and Obesity
Journal of Biological Chemistry, 2003
There is increased awareness that energy expenditure is an important component of weight control and that its dysregulation promotes obesity. This minireview will examine the role of energy expenditure in regulating fat stores, the underlying mitochondrial basis for energy expenditure, and implications of this for potential mechanisms of adaptive thermogenesis and then discuss, in detail, recent evidence regarding the important role of -adrenergic receptors in diet-induced thermogenesis and prevention of diet-induced obesity. Energy Balance Fat is stored when the number of calories consumed exceeds the number of calories expended. In principle, obesity could be caused by increased food intake or decreased energy expenditure or from a combination of the two. Indeed, most single gene mutation models of rodent obesity, whether naturally occurring or genetically engineered, have both increased food intake and decreased energy expenditure. The frequent occurrence of combined abnormalities strongly supports the view that systems exist to match energy expenditure to food intake over time and that dysfunction of both arms is required to produce massive obesity. The power and precision of this system is demonstrated by the fact that most individuals are not obese, despite the thermodynamic reality that a slight mismatch between intake and expenditure is all that is necessary to produce marked weight gain. Although components of this energy balance system have been identified, including leptin, the leptin receptor, ␣-melanocyte-stimulating hormone, the melanocortin-4 receptor, and now ARs 1 (1-6), many questions still remain. For example, what is the wiring diagram of central neural circuits regulating energy balance? Also, and relevant to this review, what are the efferent pathways, i.e. nerves and hormones, target tissues, and intracellular mechanisms, by which the brain controls energy expenditure? Evidence That Energy Expenditure Is Defective in Obesity The strongest support for defects in energy expenditure in obesity comes from monogenic rodent models such as ob/ob, db/db, and melanocortin-4 receptor gene knockout mice. When food intake of these mutant animals, deficient in either leptin, leptin receptors, or melanocortin-4 receptors, is restricted to that of wild-type controls, a maneuver termed pair feeding, marked obesity still develops (7). Animals with experimentally induced hypothalamic lesions also become obese when pair fed to sham-treated controls (8). In fact, there are few exceptions to the rule that animal models of obesity, whether genetic or lesion-induced, have decreased energy expenditure. The situation in humans is less clear. In large part, this is because of difficulties in studying heterogeneous populations, the * This minireview will be reprinted in the 2003 Minireview Compendium, which will be available in January, 2004. This is the second article of six in the "New Animal Models for Study of Metabolism'' Minireview Series.
1 Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice
Journal of Endocrinology, 2012
Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple b-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the b 1 isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the b 1 selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the b 1 gene (KO of b 1 adrenergic receptor (b 1 KO)) developed hypothermia during cold exposure and exhibited decreased iBAT thermal response to NE or DB infusion. Thirdly, when placed on a high-fat diet (HFD; 40% fat) for 5 weeks, b 1 KO mice were more susceptible to obesity than WT controls and failed to develop diet-induced thermogenesis as assessed by BAT Ucp1 mRNA levels and oxygen consumption. Furthermore, b 1 KO mice exhibited fasting hyperglycemia and more intense glucose intolerance, hypercholesterolemia, and hypertriglyceridemia when placed on the HFD, developing marked non-alcoholic steatohepatitis. In conclusion, the b 1 signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis. exposure (4 8C) for 3 h of C57 (WT) and b 1 KO; *P!0 . 05 and **P!0 . 001 vs WT; (B) oxygen consumption during decreasing temperature exposure of C57 (WT) and b1KO mice; *P!0 . 001 vs WT; (C) BAT thermogenic response to NE infusion of C57 (WT) and b1KO mice; *P!0 . 004 vs WT; (D) BAT thermogenic response during infusion of DB of C57 (WT) and b1KO mice; *P!0 . 004 vs WT; entries are meanGS.E.M. of six animals per group. b 1 in adaptive thermogenesis . C B UETA, G W FERNANDES and others 361 www.endocrinology-journals.org Journal of Endocrinology (2012) 214, 359-365 a P!0 . 001 vs WT. b P!0 . 01 vs b 1 KO. c P!0 . 001 vs WT HF.
Impaired physiological thermoregulation in postweaning obese female LA/Ntul//-cp (corpulent) rats
Advances in Obesity, Weight Management & Control, 2021
Groups of lean and obese female lean, and obese LA/Ntul//cp (corpulent) rats were subjected to measures of thermic responses to feeding, noradrenaline administration, and responses to 14 hours of cold exposure to access their capacity for thermoregulation beginning at 6 to 8 weeks of age. Body weights and adipose tissue mass were greater in the obese than the lean phenotype (p=<0.05). RMR and the dose related thermic responses to norepinephrine (NE) in lean were greater than in obese. Cold exposure at 4°C resulted in decreases in rectal but not core temperature in obese rats, and the thermic responses to 45 minutes of 4°C cold exposure on VO2 were typical but were significantly greater in lean than obese animals at all points measured. Circulating thyroid hormone concentrations were similar in lean and obese rats and T3 but not T4 increased dramatically in both phenotypes following the cold exposure, consistent with phenotype-and IBAT-linked changes in T4-5' deiodinase and thyroidal activity in this strain. These thermoregulatory changes are consistent with previous studies and may contribute to phenotype mediated aspects of energy metabolism, storage, and adipose tissue deposition and to a phenotype specific selective epigenetic propensity for the expression of obesity during the early postweaning period.
β1 Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice
Journal of Endocrinology, 2012
Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple β-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the β1isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the β1selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the β1gene (KO of β1adrenergic receptor (β1KO)) developed hypothermia during cold exposure and exhibited decreased iBAT thermal response to NE or DB infusion. Thirdly, when placed on a high-fat diet (HFD; 40% fat) for 5 weeks, β1KO mice were more susceptible to obesity than WT controls and failed to develop diet-induced thermogenesis as assessed by BATUcp1mRNA levels and oxygen consumption. Furthermore, β1KO mice exhibited fasting hyperglycemia and more intense glucos...
The effect of experimental overnutrition on nonshivering thermogenesis and obesity in LA/N-cp rats
Comparative biochemistry and physiology. A, Comparative physiology, 1991
1. Groups of congenic adult male lean and obese LA/N-cp rats were fed stock chow or the chow diet plus a cafeteria diet supplement from 4 until 6 months of age. 2. Weight gain, adipose cellularity, and adiposity were greater in obese than in lean rats and all three parameters increased more rapidly in obese than in lean rats when fed the cafeteria-supplemented diet. 3. Resting metabolic rates and basal urinary vanilylmandelic acid excretion were greater in lean than in obese rats, while serum triiodothyronine concentrations were similar in both phenotypes. The cafeteria diet was associated with significant increases in all three metabolic parameters in lean but not in obese rats. 4. The results of this study indicate that the obese phenotype of this strain has an impaired capacity for non-shivering thermogenesis (NST), in association with an enhanced propensity for development of obesity when fed stock or cafeteria diets. Moreover, the impairment in NST involves both sympathetic and...
2000
Jü rgens, Hella S., Annette Schü rmann, Reinhart Kluge, Sylvia Ortmann, Susanne Klaus, Hans-Georg Joost, and Matthias H. Tschöp. Hyperphagia, lower body temperature, and reduced running wheel activity precede development of morbid obesity in New Zealand obese mice. Among polygenic mouse models of obesity, the New Zealand obese (NZO) mouse exhibits the most severe phenotype, with fat depots exceeding 40% of total body weight at the age of 6 mo. Here we dissected the components of energy balance including feeding behavior, locomotor activity, energy expenditure, and thermogenesis compared with the related lean New Zealand black (NZB) and obese B6.V-Lep ob /J (ob/ob) strains (11% and 65% fat at 23 wk, respectively). NZO mice exhibited a significant hyperphagia that, when food intake was expressed per metabolic body mass, was less pronounced than that of the ob/ob strain. Compared with NZB, NZO mice exhibited increased meal frequency, meal duration, and meal size. Body temperature as determined by telemetry with implanted sensors was reduced in NZO mice, but again to a lesser extent than in the ob/ob strain. In striking contrast to ob/ob mice, NZO mice were able to maintain a constant body temperature during a 20-h cold exposure, thus exhibiting a functioning cold-induced thermogenesis. No significant differences in spontaneous home cage activity were observed among NZO, NZB, and ob/ob strains. When mice had access to voluntary running wheels, however, running activity was significantly lower in NZO than NZB mice and even lower in ob/ob mice. These data indicate that obesity in NZO mice, just as in humans, is due to a combination of hyperphagia, reduced energy expenditure, and insufficient physical activity. Because NZO mice differ strikingly from the ob/ob strain in their resistance to cold stress, we suggest that the molecular defects causing hyperphagia in NZO mice are located distal from leptin and its receptor. feeding behavior; polygenic obesity; ob/ob mice; thermogenesis;
PLoS ONE, 2010
Background: The OLETF rat is an animal model of early onset hyperphagia induced obesity, presenting multiple pre-obese characteristics during the suckling period. In the present study, we used a cross-fostering strategy to assess whether interactions with obese dams in the postnatal environment contributed to the development of obesity. Methodology: On postnatal Day (PND)-1 OLETF and control LETO pups were cross-fostered to same or opposite strain dams. An independent ingestion test was performed on PND11 and a nursing test on PND18. Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin, cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat pads were collected and weighed and adipocyte size and number were estimated. Body weight and intake, as well as the estrous cycle of the female offspring were monitored.