Leptin and Melanocortin Signaling Mediates Hypertension in Offspring From Female Rabbits Fed a High-Fat Diet During Gestation and Lactation

Maternal high-fat diet in rabbits leads to hypertension and elevated renal sympathetic nerve activity (RSNA) in adult offspring but whether this is due to adiposity or maternal programming is unclear. We gave intracerebroventricular (ICV) and ventromedial hypothalamus (VMH) administration of leptin-receptor antagonist, α-melanocyte-stimulating hormone (αMSH), melanocortin-receptor antagonist (SHU9119), or insulin-receptor (InsR) antagonist to conscious adult offspring from mothers fed a high-fat diet (mHFD), control diet (mCD), or mCD offspring fed HFD for 10d (mCD10d, to deposit equivalent fat but not during development). mHFD and mCD10d rabbits had higher mean arterial pressure (MAP, +6.4 mmHg, +12.1 mmHg, p < 0.001) and RSNA (+2.3 nu, +3.2 nu, p < 0.01) than mCD, but all had similar plasma leptin. VMH leptin-receptor antagonist reduced MAP (−8.0 ± 3.0 mmHg, p < 0.001) in mCD10d but not in mHFD or mCD group. Intracerebroventricular leptin-receptor antagonist reduced MAP only in mHFD rabbits (p < 0.05). Intracerebroventricular SHU9119 reduced MAP and RSNA in mHFD but only reduced MAP in the mCD10d group. VMH αMSH increased RSNA (+85%, p < 0.001) in mHFD rabbits but ICV αMSH increased RSNA in both mHFD and mCD10d rabbits (+45%, +51%, respectively, p < 0.001). The InsR antagonist had no effect by either route on MAP or RSNA. Hypothalamic leptin receptor and brain-derived neurotrophic factor (BDNF) mRNA were greater in mHFD compared with mCD rabbits and mCD10d rabbits. In conclusion, the higher MAP in mHFD and mCD10d offspring was likely due to greater central leptin signaling at distinct sites within the hypothalamus while enhanced melanocortin contribution was common to both groups suggesting that residual body fat was mainly responsible. However, the effects of SHU9119 and αMSH on RSNA pathways only in mHFD suggest a maternal HFD may program sympatho-excitatory capacity in these offspring and that this may involve increased leptin receptor and BDNF expression.

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Maternal high-fat diet programs cerebrovascular remodeling in adult rat offspring

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17731956 ◽

2017 ◽

Vol 38 (11) ◽

pp. 1954-1967 ◽

Cited By ~ 2

Author(s):

ChengCheng Lin ◽

XiaoYun Wu ◽

YuLei Zhou ◽

Bei Shao ◽

XiaoTing Niu ◽

...

Keyword(s):

High Fat Diet ◽

Maternal Diet ◽

Control Diet ◽

Endothelial Damage ◽

Adult Offspring ◽

High Fat ◽

Adult Rat ◽

Transmission Electron ◽

Pregnancy And Lactation ◽

And Function

Maternal environmental factors such as diet have consequences on later health of the offspring. We found that maternal high-fat diet (HFD) exposure renders adult offspring brain more susceptible to ischemic injury. The present study was further to investigate whether HFD consumption during rat pregnancy and lactation influences the cerebral vasculature in adult male offspring. Besides the endothelial damage observed in the transmission electron microscopy, the MCAs of offspring from fat-fed dams fed with control diet (HFD/C) also displayed increased wall thickness and media/lumen ratio, suggesting that cerebrovascular hypertrophy or hyperplasia occurs. Moreover, smaller lumen diameter and elevated myogenic tone of the MCAs over a range of intralumenal pressures indicate inward cerebrovascular remodeling in HFD/C rats, with a concomitant increase in vessel stiffness. More importantly, both wire and pressure myography demonstrated that maternal HFD intake also enhanced the MCAs contractility to ET-1, accompanied by increases in ET types A receptor (ETAR) but not B (ETBR) density in the arteries. Furthermore, ETAR antagonism but not ETBR antagonism restored maternal HFD-induced cerebrovascular dysfunction in adult offspring. Taken together, maternal diet can substantially influence adult offspring cerebrovascular health, through remodeling of both structure and function, at least partially in an ET-1 manner.

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Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00698.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. H1061-H1069 ◽

Cited By ~ 9

Author(s):

Yu-Ping Zhang ◽

Yan-Li Huo ◽

Zhi-Qin Fang ◽

Xue-Fang Wang ◽

Jian-Dong Li ◽

...

Keyword(s):

Nadph Oxidase ◽

Proinflammatory Cytokines ◽

High Fat Diet ◽

Control Diet ◽

Renin Angiotensin System ◽

Adult Offspring ◽

Ang Ii ◽

High Fat ◽

Pressor Responses ◽

The Brain

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

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Maternal high fat diet (HFD) in the adult offspring brain modifies cell density and neuronal density

Reproduction Abstracts ◽

10.1530/repabs.3.o020 ◽

2016 ◽

Author(s):

Diego Ojeda Pedraza ◽

Kate Jane-Coupe ◽

Megan Earl ◽

Oliver Hutton ◽

Judith Eckert ◽

...

Keyword(s):

Cell Density ◽

High Fat Diet ◽

Adult Offspring ◽

High Fat ◽

Neuronal Density

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Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

Scientific Reports ◽

10.1038/s41598-021-81037-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anandini Swaminathan ◽

Andrej Fokin ◽

Tomas Venckūnas ◽

Hans Degens

Keyword(s):

Skeletal Muscle ◽

Glucose Tolerance ◽

Muscle Mass ◽

Body Mass ◽

High Fat Diet ◽

Control Diet ◽

Metabolic Health ◽

High Fat ◽

Methionine Restriction ◽

Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

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Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mito-Phagy in Female Rat Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms22147551 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7551

Author(s):

Sven H. Rouschop ◽

Samantha J. Snow ◽

Urmila P. Kodavanti ◽

Marie-José Drittij ◽

Lou M. Maas ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

High Fat Diet ◽

Control Diet ◽

Ozone Exposure ◽

Female Rat ◽

Induced Responses ◽

High Fat ◽

Molecular Control ◽

Rat Offspring ◽

Oxidant Status

Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.

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Flavonoids from Mulberry Leaves Alleviate Lipid Dysmetabolism in High Fat Diet-Fed Mice: Involvement of Gut Microbiota

Microorganisms ◽

10.3390/microorganisms8060860 ◽

2020 ◽

Vol 8 (6) ◽

pp. 860 ◽

Cited By ~ 1

Author(s):

Yinzhao Zhong ◽

Bo Song ◽

Changbing Zheng ◽

Shiyu Zhang ◽

Zhaoming Yan ◽

...

Keyword(s):

Acetic Acid ◽

Lipid Metabolism ◽

Gut Microbiota ◽

High Fat Diet ◽

Control Diet ◽

Liver Steatosis ◽

High Fat ◽

Acetic Acid Production ◽

Mulberry Leaves ◽

Brown Adipose

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for six weeks. FML administration improved lipid accumulation, alleviated liver steatosis and the whitening of brown adipose tissue, and improved gut microbiota composition in HFD-fed mice. Microbiota transplantation from FML-treated mice alleviated HFD-induced lipid metabolic disorders. Moreover, FML administration restored the production of acetic acid in HFD-fed mice. Correlation analysis identified a significant correlation between the relative abundances of Bacteroidetes and the production of acetic acid, and between the production of acetic acid and the weight of selected adipose tissues. Overall, our results demonstrated that in HFD-fed mice, the lipid metabolism improvement induced by FML administration might be mediated by gut microbiota, especially Bacteroidetes-triggered acetic acid production.

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Maternal high fat diet programs stress-induced behavioral disorder in adult offspring

Physiology & Behavior ◽

10.1016/j.physbeh.2015.09.023 ◽

2015 ◽

Vol 152 ◽

pp. 119-127 ◽

Cited By ~ 13

Author(s):

ChengCheng Lin ◽

Bei Shao ◽

HuanJie Huang ◽

YuLei Zhou ◽

YuanShao Lin

Keyword(s):

High Fat Diet ◽

Behavioral Disorder ◽

Adult Offspring ◽

High Fat

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Effect of selective expression of dominant-negative PPARγ in pro-opiomelanocortin neurons on the control of energy balance

Physiological Genomics ◽

10.1152/physiolgenomics.00032.2016 ◽

2016 ◽

Vol 48 (7) ◽

pp. 491-501 ◽

Cited By ~ 9

Author(s):

Madeliene Stump ◽

Deng-Fu Guo ◽

Ko-Ting Lu ◽

Masashi Mukohda ◽

Xuebo Liu ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Energy Balance ◽

High Fat Diet ◽

Control Diet ◽

Cre Recombinase ◽

Dominant Negative ◽

High Fat ◽

Pparγ Agonist ◽

The Brain

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.

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