Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

2005 ◽  
Vol 288 (6) ◽  
pp. E1236-E1243 ◽  
Author(s):  
Elena Velkoska ◽  
Timothy J. Cole ◽  
Margaret J. Morris
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Neuropeptide Y ◽  
Litter Size ◽  
High Fat Diet ◽  
Dietary Intervention ◽  
High Fat ◽  
Brown Adipose

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.

scholarly journals Engineered human brown adipocyte microtissues improved glucose and insulin homeostasis in high fat diet-induced obese and diabetic mice

2021 ◽  
Author(s):  
Ou Wang ◽  
Li Han ◽  
Haishuang Lin ◽  
Mingmei Tian ◽  
Shuyang Zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
High Fat ◽  
Brown Adipose ◽  
Insulin Homeostasis ◽  
Human And Mouse

AbstractA large population of people is affected by obesity (OB) and its associated type 2 diabetes mellitus(T2DM). There are currently no safe and long-lasting anti-OB/T2DM therapies. Clinical data and preclinical transplantation studies show that transplanting metabolically active brown adipose tissue (BAT) is a promising approach to prevent and treat OB and its associated metabolic and cardiovascular diseases. However, most transplantation studies used mouse BAT, and it is uncertain whether the therapeutic effect would be applied to human BAT since human and mouse BATs have distinct differences. Here, we report the fabrication of three-dimensional (3D) human brown adipose microtissues, their survival and safety, and their capability to improve glucose and insulin homeostasis and manage body weight gain in high-fat diet (HFD)-induced OB and diabetic mice.Methods3D BA microtissues were fabricated and transplanted into the kidney capsule of Rag1-/- mice. HFD was initiated to induce OB 18 days after transplantation. A low dose of streptozotocin (STZ) was administrated after three month’s HFD to induce diabetes. The body weight, fat and lean mass, plasma glucose level, glucose tolerance and insulin sensitivity were recorded regularly. In addition, the levels of human and mouse adipokines in the serum were measured, and various tissues were harvested for histological and immunostaining analyses.ResultsWe showed that 3D culture promoted BA differentiation and uncoupling protein-1 (UCP-1) protein expression, and the microtissue size significantly influenced the differentiation efficiency and UCP-1 protein level. The optimal microtissue diameter was about 100 µm. Engineered 3D BA microtissues survived for the long term with angiogenesis and innervation, alleviated body weight and fat gain, and significantly improved glucose tolerance and insulin sensitivity. They protected the endogenous BAT from whitening and reduced mouse white adipose tissue (WAT) hypertrophy and liver steatosis. In addition, the microtissues secreted soluble factors and modulated the expression of mouse adipokines. We also showed that scaling up the microtissue production could be achieved using the 3D suspension culture or a 3D thermoreversible hydrogel matrix. Further, these microtissues can be preserved at room temperature for 24 hours or be cryopreserved for the long term without significantly sacrificing cell viability.ConclusionOur study showed that 3D BA microtissues could be fabricated at large scales, cryopreserved for the long term, and delivered via injection. BAs in the microtissues had higher purity, and higher UCP-1 protein expression than BAs prepared via 2D culture. In addition, 3D BA microtissues had good in vivo survival and tissue integration, and had no uncontrolled tissue overgrowth. Furthermore, they showed good efficacy in preventing OB and T2DM with a very low dosage compared to literature studies. Thus, our results show engineered 3D BA microtissues are promising anti-OB/T2DM therapeutics. They have considerable advantages over dissociated BAs or BAPs for future clinical applications in terms of product scalability, storage, purity, quality, and in vivo safety, dosage, survival, integration, and efficacy.

scholarly journals The Role of Neuropeptide Y in Adipocyte-Macrophage Crosstalk during High Fat Diet-Induced Adipose Inflammation and Liver Steatosis

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1739
Author(s):  
Seongjoon Park ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
Isao Shimokawa
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Neuropeptide Y ◽  
Mrna Expression ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Brown Adipose ◽  
Adipose Inflammation

Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY−/− mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD.

Ventromedial hypothalamic knife-cut lesions in rats resistant to dietary obesity

1984 ◽  
Vol 246 (6) ◽  
pp. R943-R948 ◽  
Author(s):  
J. Oku ◽  
G. A. Bray ◽  
J. S. Fisler ◽  
R. Schemmel
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
High Fat Diet ◽  
Corn Oil ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Dietary Obesity

The effects of ventromedial hypothalamic (VMH) knife-cut lesions on food intake and body weight of S 5B/Pl rats, which are normally resistant to obesity when eating a high-fat diet, were examined in two experiments. In the first experiment body weight increased only slightly after VMH knife-cut lesions when animals were fed pelleted laboratory chow or a 10% corn oil diet. When eating the 30% corn oil diet, however, body weight increased in the VMH knife-cut rats. In the second experiment VMH knife-cut lesions produced a small weight gain in rats fed the 10% fat diet; this manipulation also increased food intake and disrupted the normal diurnal feeding pattern. Changes in the weight of the liver, interscapular brown adipose tissue, and white adipose tissue paralleled the changes in body weight. Plasma insulin increased in the rats eating the 30% corn oil diet ad libitum but not in the VMH-lesioned animals pair fed to the sham-operated rats. Incorporation of 3H from 3H2O into lipid was significantly increased in white fat of animals with VMH knife cuts. Similar results were obtained from incubation of adipose tissue in vitro with insulin and radioactively labeled glucose. These studies show that hypothalamic knife-cut lesions can remove the resistance of the S 5B/Pl rats to obesity when they are fed a high-fat diet.

scholarly journals Cannabinoid Type 1 (CB1) Receptors on Sim1-Expressing Neurons Regulate Energy Expenditure in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 411-418 ◽  
Author(s):  
Pierre Cardinal ◽  
Luigi Bellocchio ◽  
Omar Guzmán-Quevedo ◽  
Caroline André ◽  
Samantha Clark ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Cb1 Receptor ◽  
Cb1 Receptors ◽  
High Fat ◽  
Brown Adipose

The paraventricular nucleus of the hypothalamus (PVN) regulates energy balance by modulating not only food intake, but also energy expenditure (EE) and brown adipose tissue thermogenesis. To test the hypothesis that cannabinoid type 1 (CB1) receptor in PVN neurons might control these processes, we used the Cre/loxP system to delete CB1 from single-minded 1 (Sim1) neurons, which account for the majority of PVN neurons. On standard chow, mice lacking CB1 receptor in Sim1 neurons (Sim1-CB1-knockout [KO]) had food intake, body weight, adiposity, glucose metabolism, and EE comparable with wild-type (WT) (Sim1-CB1-WT) littermates. However, maintenance on a high-fat diet revealed a gene-by-diet interaction whereby Sim1-CB1-KO mice had decreased adiposity, improved insulin sensitivity, and increased EE, whereas feeding behavior was similar to Sim1-CB1-WT mice. Additionally, high-fat diet-fed Sim1-CB1-KO mice had increased mRNA expression of the β3-adrenergic receptor, as well as of uncoupling protein-1, cytochrome-c oxidase subunit IV and mitochondrial transcription factor A in the brown adipose tissue, all molecular changes suggestive of increased thermogenesis. Pharmacological studies using β-blockers suggested that modulation of β-adrenergic transmission play an important role in determining EE changes observed in Sim1-CB1-KO. Finally, chemical sympathectomy abolished the obesity-resistant phenotype of Sim1-CB1-KO mice. Altogether, these findings reveal a diet-dependent dissociation in the CB1 receptor control of food intake and EE, likely mediated by the PVN, where CB1 receptors on Sim1-positive neurons do not impact food intake but hinder EE during dietary environmental challenges that promote body weight gain.

Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

2009 ◽  
Vol 297 (1) ◽  
pp. E184-E193 ◽  
Author(s):  
Josep Mercader ◽  
Joan Ribot ◽  
Incoronata Murano ◽  
Søren Feddersen ◽  
Saverio Cinti ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Retinoblastoma Protein ◽  
Brown Adipocyte ◽  
Wild Type ◽  
High Fat ◽  
Brown Adipose

Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ line haploinsufficiency of the pRb gene (Rb) on the response to high-fat diet feeding in mice. Rb+/− mice had body weight and adiposity indistinguishable from that of wild-type (Rb+/+) littermates when maintained on a standard diet, yet they gained less body weight and body fat after long-term high-fat diet feeding coupled with reduced feed efficiency and increased rectal temperature. Rb haploinsufficiency ameliorated insulin resistance and hepatosteatosis after high-fat diet in male mice, in which these disturbances were more marked than in females. Compared with wild-type littermates, Rb+/− mice fed a high-fat diet displayed higher expression of peroxisome proliferator-activated receptor (PPAR)γ as well as of genes involved in mitochondrial function, cAMP sensitivity, brown adipocyte determination, and tissue vascularization in white adipose tissue depots. Furthermore, Rb+/− mice exhibited signs of enhanced activation of brown adipose tissue and higher expression levels of PPARα in liver and of PPARδ in skeletal muscle, suggestive of an increased capability for fatty acid oxidation in these tissues. These findings support a role for pRb in modulating whole body energy metabolism and the plasticity of the adipose tissues in vivo and constitute first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances.

scholarly journals Ellagic Acid Affects Metabolic and Transcriptomic Profiles and Attenuates Features of Metabolic Syndrome in Adult Male Rats

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 804
Author(s):  
Adéla Kábelová ◽  
Hana Malínská ◽  
Irena Marková ◽  
Olena Oliyarnyk ◽  
Blanka Chylíková ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Ellagic Acid ◽  
High Fat Diet ◽  
Male Rats ◽  
High Fat ◽  
Brown Adipose

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet–ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet–control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.

Seasonal obesity in Syrian hamsters: effects of age, diet, photoperiod, and melatonin

1984 ◽  
Vol 247 (2) ◽  
pp. R328-R334 ◽  
Author(s):  
G. N. Wade ◽  
T. J. Bartness
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Reproductive Function ◽  
Fat Content ◽  
High Fat ◽  
Melatonin Treatment ◽  
Tissue Weight ◽  
Adipose Tissue Weight ◽  
Brown Adipose

Two experiments examined the effects of photoperiod, melatonin, and diet on body weight in female Syrian hamsters (Mesocricetus auratus). In experiment 1, daily injections of 25 micrograms melatonin increased body weight when given 3 h before lights-out but not when given at the midpoint of the light phase, in a 16-h light-8-h dark cycle (LD 16:8). Ten micrograms of melatonin, given 3 h before lights-out, were sufficient to increase body weight and fat content, to increase interscapular brown adipose tissue weight, to decrease uterine weight, and to interrupt estrous cyclicity. However, 2.5 micrograms of melatonin increased body weight and fat content without affecting brown adipose tissue weight or reproductive function. In experiment 2, melatonin treatment, exposure to a short photoperiod (LD 8:16), and feeding a high-fat diet increased body weight gain in weanling (25-day-old) female hamsters. When melatonin treatment or high-fat diet were withdrawn, hamsters reduced their food intake, and their body weight and fat content returned to control levels. After 15-17 wk in the short photoperiod, hamsters also began to undereat, and their body weight and fat content returned to control levels. These findings suggest several conclusions. 1) As with the changes in reproductive function, melatonin is effective at increasing body weight only when given at certain times of day. 2) Not all end points are equally responsive to melatonin, suggesting that they are independent of one another. 3) Weanling hamsters respond to photoperiod, melatonin, and diet just as adults do. 4) The striking obesities induced by these manipulations are completely reversible.

scholarly journals Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet–Fed Mice through Increased Thermogenesis

2020 ◽  
Vol 150 (8) ◽  
pp. 2131-2138 ◽  
Author(s):  
Fang Zhou ◽  
Jielong Guo ◽  
Xue Han ◽  
Yunxiao Gao ◽  
Qimin Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
The Body ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Polyphenolic Extract ◽  
Brown Adipose

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.

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