Effects of neonatal sympathectomy on brown fat development and susceptibility to high fat diet induced obesity in mice

1991 ◽  
Vol 69 (12) ◽  
pp. 1868-1874 ◽  
Author(s):  
M. Desautels ◽  
R. A. Dulos

Injections of 6-hydroxydopamine in mouse neonates caused extensive and long lasting damage to the sympathetic nervous system and impaired brown fat development. Brown adipose tissue (BAT) thermogenic capacity of sympathectomized mice (up to 120 days old) was reduced because of marked reductions in the tissue mitochondrial protein content and the mitochondrial concentration of uncoupling protein, as assessed by [3H]GDP binding and immunoassay. Neonatal sympathectomy did not affect BAT DNA content. Sympathectomized mice also had reduced epinephrine-stimulated rates of oxygen consumption. BAT of sympathectomized mice failed to respond by increases in [3H]GDP binding to isolated mitochondria and uncoupling protein concentration when animals were offered a palatable high-fat dietary supplement that increased calorie intake of both normal and sympathectomized mice. The high-fat diet caused increases in body weight, carcass fat, and gonadal white fat pad weights in sympathectomized animals that were similar to those of control mice. These results show that inactivation of BAT metabolism did not accentuate the development of obesity caused by a dietary supplement rich in fat and suggest that stimulation of BAT metabolism was not very effective in counteracting the obesity-inducing effect of this diet.Key words: body weight, body temperature, energy balance, mitochondria, uncoupling protein.


Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1457-1466 ◽  
Author(s):  
Miyuki Shibata ◽  
Ryoichi Banno ◽  
Mariko Sugiyama ◽  
Takashi Tominaga ◽  
Takeshi Onoue ◽  
...  

Abstract Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.



2020 ◽  
Vol 150 (8) ◽  
pp. 2131-2138 ◽  
Author(s):  
Fang Zhou ◽  
Jielong Guo ◽  
Xue Han ◽  
Yunxiao Gao ◽  
Qimin Chen ◽  
...  

ABSTRACT Background Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. Objectives In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)–fed obese mice. Methods The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. Results After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. Conclusions Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.



2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.



2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jihye Lee ◽  
Seong-Ho Lee

Abstract Objectives Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin. Recently, we observed that patchouli alcohol reduced lipid accumulation in differentiated 3T3-L1 adipocytes and increased glucose uptake in differentiated C2C12 myocytes. This study was designed to investigate anti-obese and anti-diabetic activities of patchouli alcohol using high fat diet-induced obese mouse model. Methods Forty-eight 5-week old C57BL/6 J male mice were assigned into four groups and fed with 1) normal diet (control), 2) high fat diet, 3) high fat diet with gavaging 25 mg of patchouli alcohol/kg body weight and 4) high fat diet with gavaging 50 mg of patchouli alcohol/kg body weight. High fat diet or control diets were provided to each treatment group for four weeks and then different doses of patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered for following 8 weeks with the diet. At age of week 17, all animals were sacrificed, fat tissues were collected, and tissue weight was measured. In addition, twenty C57BL/6 J male mice were assigned into the same treatment groups above. At the end of the 8 weeks (age of week 17), the mice were fasted for 12 h and the oral glucose tolerance test was performed after intraperitoneal injection of 2 g of anhydrous glucose/kg body weight. The blood was collected from tail at 0, 15, 30, 90 and 120 min after injection and blood glucose level was analyzed using glucose meter. Results Treatment of patchouli alcohol (50 mg/kg body weight) significantly reduced body weight and accumulation of body fat pads which was highly induced by feeding of high fat diet. An analysis of individual fat pad weights (expressed as mg weight of fat pad/g body weight) revealed a significant decrease of epididymal and retroperitoneal fat pad in patchouli alcohol-treated mice whereas brown adipose tissue were not significantly altered. And, slightly improved glucose tolerance was observed at 90 and 120 minutes after glucose injection in mice treated with patchouli alcohol (50 mg/kg body weight) compared to those fed with high fat diet alone. Conclusions We propose a potential use of patchouli alcohol as an anti-obesity compound in obese population. Funding Sources NIFA Hatch grant. Supporting Tables, Images and/or Graphs



1987 ◽  
Vol 252 (2) ◽  
pp. R402-R408 ◽  
Author(s):  
T. Yoshida ◽  
J. S. Fisler ◽  
M. Fukushima ◽  
G. A. Bray ◽  
R. A. Schemmel

The effects of dietary fat content, lighting cycle, and feeding time on norepinephrine turnover in interscapular brown adipose tissue, heart, and pancreas, and on blood 3-hydroxybutyrate, serum glucose, insulin, and corticosterone have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to dietary obesity, have a more rapid turnover of norepinephrine in interscapular brown adipose tissue and heart and a greater increase in the concentration of norepinephrine in brown fat when eating a high-fat diet than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. Light cycle and feeding schedule are important modulators of sympathetic activity in heart and pancreas but not in brown fat. Rats of the resistant strain also have higher blood 3-hydroxybutyrate concentrations and lower insulin and corticosterone levels than do rats of the susceptible strain. A high-fat diet increases 3-hydroxybutyrate concentrations and reduces insulin levels in both strains. These studies show, in rats eating a high-fat diet, that differences in norepinephrine turnover, particularly in brown adipose tissue, may play an important role in whether dietary obesity develops and in the manifestations of resistance to this phenomenon observed in the S 5B/Pl rat.



1986 ◽  
Vol 251 (1) ◽  
pp. E8-E13 ◽  
Author(s):  
J. Kopecky ◽  
L. Sigurdson ◽  
I. R. Park ◽  
J. Himms-Hagen

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.



2017 ◽  
Vol 45 (04) ◽  
pp. 813-832 ◽  
Author(s):  
Hyeon-Jeong Kim ◽  
Sanghwa Kim ◽  
Ah Young Lee ◽  
Yoonjeong Jang ◽  
Orkhonselenge Davaadamdin ◽  
...  

This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500[Formula: see text]mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.



2005 ◽  
Vol 288 (6) ◽  
pp. E1236-E1243 ◽  
Author(s):  
Elena Velkoska ◽  
Timothy J. Cole ◽  
Margaret J. Morris

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.



2017 ◽  
Vol 313 (5) ◽  
pp. R535-R548 ◽  
Author(s):  
Jonathan Weng ◽  
Danwen Lou ◽  
Stephen C. Benoit ◽  
Natalie Coschigano ◽  
Stephen C. Woods ◽  
...  

Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.



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