scholarly journals STAT5 ablation in AgRP neurons increases female adiposity and blunts food restriction adaptations

2020 ◽  
Vol 64 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Isadora C Furigo ◽  
Pryscila D S Teixeira ◽  
Paula G F Quaresma ◽  
Naira S Mansano ◽  
Renata Frazão ◽  
...  
Keyword(s):  
Food Intake ◽  
Mrna Expression ◽  
Body Fat ◽  
Glucose Homeostasis ◽  
Knockout Mice ◽  
Food Restriction ◽  
Energy Homeostasis ◽  
Metabolic Effects ◽  
Control Group ◽  
Female Mice

AgRP neurons are important players in the control of energy homeostasis and are responsive to several hormones. In addition, STAT5 signalling in the brain, which is activated by metabolic hormones and growth factors, modulates food intake, body fat and glucose homeostasis. Given that, and the absence of studies that describe STAT5 function in AgRP cells, the present study investigated the metabolic effects of Stat5a/b gene ablation in these neurons. We observed that STAT5 signalling in AgRP neurons regulates body fat in female mice. However, male and female STAT5-knockout mice did not exhibit altered food intake, energy expenditure or glucose homeostasis compared to control mice. The counter-regulatory response or glucoprivic hyperphagia induced by 2-deoxy-d-glucose treatment were also not affected by AgRP-specific STAT5 ablation. However, under 60% food restriction, AgRP STAT5-knockout mice had a blunted upregulation of hypothalamic Agrp mRNA expression and corticosterone serum levels compared to control mice, suggesting a possible role for STAT5 in AgRP neurons for neuroendocrine adaptations to food restriction. Interestingly, ad libitum fed knockout male mice had reduced Pomc and Ucp-1 mRNA expression compared to control group. Taken together, these results suggest that STAT5 signalling in AgRP neurons regulates body adiposity in female mice, as well as some neuroendocrine adaptations to food restriction.

Loss of body fat in lean parabiotic partners of ob/ob mice

1997 ◽  
Vol 272 (6) ◽  
pp. R1809-R1815 ◽  
Author(s):  
R. B. Harris
Keyword(s):  
Food Intake ◽  
Mrna Expression ◽  
Body Fat ◽  
Rectal Temperature ◽  
Serum Insulin ◽  
Serum Leptin ◽  
Leptin Expression

The objective of this experiment was to confirm whether changes in serum leptin and leptin expression were consistent with it being the "lipostatic" factor implicated by earlier parabiosis studies. Lean (+/?) and obese (ob/ob) female C57B1/6J-ob mice were parabiosed (lean-ob/ob) at 7 wk of age. Controls were ob/ob-ob/ob and lean-lean pairs, and single lean and ob/ob mice. Pairs were maintained for 50 days. In ob/ob members of lean-ob/ob pairs serum insulin was normalized, food intake was suppressed, and body fat was reduced by 14%. Lean partners of ob/ob mice had a reduced rectal temperature and experienced a 37% reduction in body fat. Despite loss of fat, serum leptin and adipose leptin mRNA expression were unchanged in lean partners of ob/ob mice. These results suggest that, in lean-ob/ob parabiotic pairs, the ob/ob mouse responds to leptin originating in the lean parabiont, whereas the lean partner responds to a circulating signal, originating in the ob/ob mouse, that maintains leptin expression at inappropriate levels for the degree of adiposity of the lean animal.

Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake

1999 ◽  
Vol 276 (4) ◽  
pp. R1172-R1179 ◽  
Author(s):  
James P. DeLany ◽  
Fawn Blohm ◽  
Alycia A. Truett ◽  
Joseph A. Scimeca ◽  
David B. West
Keyword(s):  
Body Composition ◽  
Linoleic Acid ◽  
Food Intake ◽  
Conjugated Linoleic Acid ◽  
Energy Intake ◽  
Body Fat ◽  
Metabolic Effects ◽  
Protein Accumulation ◽  
High Fat ◽  
Fat Accumulation

Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice ( n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.

scholarly journals The effects of physiological adaptations to calorie restriction on global cell proliferation rates

2011 ◽  
Vol 300 (4) ◽  
pp. E735-E745 ◽  
Author(s):  
Matthew D. Bruss ◽  
Airlia C. S. Thompson ◽  
Ishita Aggarwal ◽  
Cyrus F. Khambatta ◽  
Marc K. Hellerstein
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Body Fat ◽  
Calorie Restriction ◽  
Percent Body Fat ◽  
Female Mice ◽  
Physiological Adaptations ◽  
Running Wheels

Calorie restriction (CR) reduces the rate of cell proliferation in mitotic tissues. It has been suggested that this reduction in cell proliferation may mediate CR-induced increases in longevity. However, the mechanisms that lead to CR-induced reductions in cell proliferation rates remain unclear. To evaluate the CR-induced physiological adaptations that may mediate reductions in cell proliferation rates, we altered housing temperature and access to voluntary running wheels to determine the effects of food intake, energy expenditure, percent body fat, and body weight on proliferation rates of keratinocytes, liver cells, mammary epithelial cells, and splenic T-cells in C57BL/6 mice. We found that ∼20% CR led to a reduction in cell proliferation rates in all cell types. However, lower cell proliferation rates were not observed with reductions in 1) food intake and energy expenditure in female mice housed at 27°C, 2) percent body fat in female mice provided running wheels, or 3) body weight in male mice provided running wheels compared with ad libitum-fed controls. In contrast, reductions in insulin-like growth factor I were associated with decreased cell proliferation rates. Taken together, these data suggest that CR-induced reductions in food intake, energy expenditure, percent body fat, and body weight do not account for the reductions in global cell proliferation rates observed in CR. In addition, these data are consistent with the hypothesis that reduced cell proliferation rates could be useful as a biomarker of interventions that increase longevity.

scholarly journals Sex Differences in Energy Metabolism Need to Be Considered with Lifestyle Modifications in Humans

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Betty N. Wu ◽  
Anthony J. O'Sullivan
Keyword(s):  
Sex Differences ◽  
Energy Metabolism ◽  
Body Fat ◽  
Sex Steroids ◽  
Energy Homeostasis ◽  
Energy Restriction ◽  
Metabolic Effects ◽  
Lifestyle Modifications ◽  
The Relationship

Women have a higher proportion of body fat compared to men. However, women consume fewer kilojoules per kilogram lean mass and burn fat more preferentially during exercise compared with men. During gestation, women store even greater amounts of fat that cannot be solely attributed to increased energy intake. These observations suggest that the relationship between kilojoules consumed and kilojoules utilised is different in men and women. The reason for these sex differences in energy metabolism is not known; however, it may relate to sex steroids, differences in insulin resistance, or metabolic effects of other hormones such as leptin. When considering lifestyle modifications, sex differences in energy metabolism should be considered. Moreover, elucidating the regulatory role of hormones in energy homeostasis is important for understanding the pathogenesis of obesity and perhaps in the future may lead to ways to reduce body fat with less energy restriction.

scholarly journals Inconsistencies in the assessment of food intake

2012 ◽  
Vol 303 (12) ◽  
pp. E1408-E1418 ◽  
Author(s):  
Stephen C. Woods ◽  
Wolfgang Langhans
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Body Fat ◽  
Energy Homeostasis ◽  
Behavioral Responses ◽  
Normal Function ◽  
Direct Proportion ◽  
Heated Debate ◽  
The Brain ◽  
Reducing Energy

Many peptides and other compounds that influence metabolism also influence food intake, and numerous hypotheses explaining the observed effects in terms of energy homeostasis have been suggested over the years. For example, cholecystokinin (CCK), a duodenal peptide secreted during meals that aids in digestion, also reduces ongoing food intake, thereby contributing to satiation; and insulin and leptin, hormones secreted in direct proportion to body fat, act in the brain to help control adiposity by reducing energy intake. These behavioral actions are often considered to be hard-wired, such that negative experiments, in which an administered compound fails to have its purported effect, are generally disregarded. In point of fact, failures to replicate the effects of compounds on food intake are commonplace, and this occurs both between and within laboratories. Failures to replicate have historically fueled heated debate about the efficacy and/or normal function of one or another compound, leading to confusion and ambiguity in the literature. We review these phenomena and their implications and argue that, rather than eliciting hard-wired behavioral responses in the maintenance of homeostasis, compounds that alter food intake are subjected to numerous influences that can render them completely ineffective at times and that a major reason for this variance is that food intake is not under stringent homeostatic control.

scholarly journals Rho-kinase mediates the anorexigenic action of melanocortin by suppressing AMPK

2019 ◽  
Author(s):  
Sang Soo Kim ◽  
Won Min Hwang ◽  
Won-Mo Yang ◽  
Hyon Lee ◽  
Kyong Soo Park ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Rho Kinase ◽  
Metabolic Effects ◽  
Chow Diet ◽  
Physical Interaction ◽  
Signaling Mechanism ◽  
Ampk Signaling ◽  
Normal Chow

ABSTRACTObjectiveMelanocortin action is essential for the maintenance of energy homeostasis. However, knowledge of the signaling mechanism(s) that mediates the effect of melanocortin remains incomplete.MethodsROCK1 is a key regulator of energy balance in the hypothalamus. To explore the role of ROCK1 in the anorexigenic action of melanocortin, we deleted ROCK1 in MC4R neurons in mice. Next, we studied the metabolic effects of MC4R neuron-specific ROCK1-deficiency and following treatment with α-melanocyte-stimulating hormone (MSH).ResultsHere we show that α-MSH increases Rho-kinase 1 (ROCK1) activity in the hypothalamus. Deficiency of ROCK1 in MC4R-expressing neurons results in increased body weight in mice fed normal chow diet. This is likely due to increased food intake and decreased energy expenditure. Importantly, we find that ROCK1 activation in MC4R expressing neurons is required for melanocortin action, as evidenced by the fact that α– MSH’s ability to suppress food intake is impaired in MC4R neuron-specific ROCK1-deficient mice. To elucidate the mechanism by which ROCK1 mediates melanocortin action, we performedin vitrostudies in hypothalamic cells expressing MC4R. We demonstrate that α–MSH promotes the physical interaction of ROCK1 and Gα12, and this results in suppression of AMPK activity.ConclusionsOur study identifies ROCK1 as a novel mediator of melanocortin’s anorexigenic action and uncover a new MC4R→Gα12→ROCK1→AMPK signaling pathway. Targeting Rho-kinase in MC4R-expressing neurons could provide a new strategy to combat obesity and its related complications.

scholarly journals Metabolic Effects of Cortisone Acetate vs Hydrocortisone in Patients With Secondary Adrenal Insufficiency

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Elise Ekstrand ◽  
Daniela Esposito ◽  
Oskar Ragnarsson ◽  
Jörgen Isgaard ◽  
Gudmundur Johannsson
Keyword(s):  
Waist Circumference ◽  
Adrenal Insufficiency ◽  
Body Fat ◽  
Equivalent Dose ◽  
Cortisone Acetate ◽  
Metabolic Effects ◽  
Control Group ◽  
Secondary Adrenal Insufficiency ◽  
Control Groups ◽  
Switch Group

Abstract Context Pharmacokinetic properties of cortisone acetate (CA) and hydrocortisone (HC) differ because CA needs to be converted into cortisol to become active. Objective This work analyzed the metabolic consequences of switching CA to an equivalent daily dose of HC in patients with secondary adrenal insufficiency (SAI). Design This was a post hoc analysis from a prospective study including individuals with hypopituitarism receiving growth hormone replacement. Data were collected before and after a switch from CA to an equivalent dose of HC (switch group). Two control groups were included: patients continuing CA replacement (CA control group) and adrenal-sufficient hypopituitary patients (AS control group). Results The analysis included 229 patients: 105, 31, and 93 in the switch, CA control, and AS control groups, respectively. After the change from CA to HC, increases in mean body weight (1.2 kg; P < .05), waist circumference (2.9 cm; P < .001), body fat measured by dual-energy x-ray absorptiometry (1.3 kg; P < .001), and glycated hemoglobin (0.3%; P < .05) were recorded in the switch group. The increase in mean waist circumference was greater than in the AS control group (0.9 cm; P < .05). Mean body fat increased in the switch group but not in the CA control group (–0.7 kg; P < .05). Conclusions A switch from CA to an equivalent dose of HC was associated with a worsened metabolic profile, suggesting that HC has a more powerful metabolic action than CA based on the assumption that 20 mg HC equals 25 mg CA.

scholarly journals Body composition and food intake in elderly women subjected to resistance training

2001 ◽  
Vol 14 (3) ◽  
pp. 177-183
Author(s):  
Aline Rodrigues BARBOSA ◽  
José Maria SANTARÉM ◽  
Wilson JACOB FILHO ◽  
Maria de Fátima Nunes MARUCCI
Keyword(s):  
Body Composition ◽  
Resistance Training ◽  
Food Intake ◽  
Training Program ◽  
Body Fat ◽  
Elderly Women ◽  
Whole Body ◽  
Control Group ◽  
Body Fat Percentage ◽  
Fat Percentage

This study analyzed the effects of a 10-wk resistance training program on body composition in 11 elderly women (68.91 ± 5.43 yrs). A control group of 8 women (65.13 ± 4.09 yrs) served as inactive control. The body fat percentage (skinfold thickness and bioelectrical impedance), body-circumference measurements and sum of skinfolds were assessed before and after 10 weeks. Food intake was assessed immediately before week 0 and week 10, from 3-day diet records (energy, protein, carbohydrate and fat). After initial tests, the subjects began a training program consisting of eight exercises for the whole body. The training program only resulted in decrease in sum of skinfolds (p<=0.05). No significant changes in any variable were observed in the control group. In conclusion, the training program did not reduce body fat percentage, although it reduced sum of skinfolds.

scholarly journals Corticotropin-Releasing Hormone-Mediated Pathway of Leptin to Regulate Feeding, Adiposity, and Uncoupling Protein Expression in Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3547-3554 ◽  
Author(s):  
Takayuki Masaki ◽  
Go Yoshimichi ◽  
Seiichi Chiba ◽  
Tohru Yasuda ◽  
Hitoshi Noguchi ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Mrna Expression ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Hypothalamic Nucleus ◽  
Fat Cell ◽  
Brown Adipose

Abstract To examine the functional role of CRH in the regulation of energy homeostasis by leptin, we measured the effects of the CRH antagonist, α-helical CRH 8–41 (αCRH) on a number of factors affected by leptin activity. These included food intake, body weight, hypothalamic c-fos-like immunoreactivity (c-FLI), weight and histological characterization of white adipose tissue, and mRNA expressions of uncoupling protein (UCP) in brown adipose tissue (BAT) in C57Bl/6 mice. Central infusion of leptin into the lateral cerebroventricle (icv) caused significant induction of c-FLI in the paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMH), dorsomedial hypothalamic nucleus, and arcuate nucleus. In all these nuclei, the effect of leptin on expression of cFLI in the PVN and VMH was decreased by treatment with αCRH. Administration of leptin markedly decreased cumulative food intake and body weight with this effect being attenuated by pretreatment with αCRH. In peripheral tissue, leptin up-regulated BAT UCP1 mRNA expression and reduced fat depositions in this tissue. Those changes in BAT were also decreased by treatment with αCRH. As a consequence of the effects on food intake or energy expenditure, treatment with αCRH attenuated the leptin-induced reduction of body adiposity, fat cell size, triglyceride contents, and ob mRNA expression in white adipose tissue. Taken together, these results indicate that CRH neurons in the PVN and VMH may be an important mediator for leptin that contribute to regulation of feeding, adiposity, and UCP expression.

scholarly journals Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats

2005 ◽  
Vol 35 (2) ◽  
pp. 381-390 ◽  
Author(s):  
C E de Rijke ◽  
J J G Hillebrand ◽  
L A W Verhagen ◽  
T A P Roeling ◽  
R A H Adan
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Mrna Expression ◽  
Food Restriction ◽  
Wheel Running ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Energy Status ◽  
Hypothalamic Area ◽  
Expression Levels

When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.

Sign in / Sign up

Export Citation Format

Share Document