scholarly journals Time-restricted feeding protects the blood pressure circadian rhythm in diabetic mice

2021 ◽  
Vol 118 (25) ◽  
pp. e2015873118
Author(s):  
Tianfei Hou ◽  
Wen Su ◽  
Marilyn J. Duncan ◽  
Vsevolozhskaya A. Olga ◽  
Zhenheng Guo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Food Intake ◽  
Active Phase ◽  
Diabetic Patients ◽  
Chow Diet ◽  
Dark Phase ◽  
Restricted Feeding ◽  
Normal Chow

The quantity and quality of food intake have been considered crucial for peoples' wellness. Only recently has it become appreciated that the timing of food intake is also critical. Nondipping blood pressure (BP) is prevalent in diabetic patients and is associated with increased cardiovascular events. However, the causes and mechanisms of nondipping BP in diabetes are not fully understood. Here, we report that food intake and BP were arrhythmic in diabetic db/db mice fed a normal chow diet ad libitum. Imposing a food intake diurnal rhythm by time-restricted feeding (TRF; food was only available for 8 h during the active phase) prevented db/db mice from developing nondipping BP and effectively restored the already disrupted BP circadian rhythm in db/db mice. Interestingly, increasing the time of food availability from 8 h to 12 h during the active dark phase in db/db mice prompted isocaloric feeding and still provided robust protection of the BP circadian rhythm in db/db mice. In contrast, neither 8-h nor 12-h TRF affected BP dipping in wild-type mice. Mechanistically, we demonstrate that TRF protects the BP circadian rhythm in db/db mice via suppressing the sympathetic activity during the light phase when they are inactive and fasting. Collectively, these data reveal a potentially pivotal role of the timing of food intake in the prevention and treatment of nondipping BP in diabetes.

scholarly journals Active Time-Restricted Feeding Protects the Blood Pressure Circadian Rhythm in Diabetic Mice

2020 ◽  
Author(s):  
Tianfei Hou ◽  
Wen Su ◽  
Marilyn J. Duncan ◽  
Vsevolozhskaya A. Olga ◽  
Zhenheng Guo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Food Intake ◽  
Diurnal Rhythm ◽  
Vascular Tone ◽  
Restricted Feeding ◽  
Active Time ◽  
Total Calorie

AbstractThe quantity and quality of food intake have been considered crucial for peoples’ wellness. Only recently has it become appreciated that the timing of food intake, independent of total calorie consumption, is also critical. The involvement and contribution of the timing of food intake in nondipping blood pressure (BP), the most common disruption of the BP circadian rhythm in diabetes, however, remains uncertain. Here, we demonstrate that the loss of diurnal rhythm in food intake coincided with nondipping BP in type 2 diabetic db/db mice, and imposing a food intake diurnal rhythm by active time-restricted feeding (ATRF) remarkably prevented db/db mice from the development of nondipping BP. Moreover, ATRF, independent of calorie restriction, also effectively restored the already disrupted BP circadian rhythm in db/db mice. Mechanistically, ATRF reduced the sympathetic vascular tone and BP during the light phase via fasting, thus protecting the BP circadian rhythm in db/db mice. Moreover, we identified BMAL1, an obligatory core clock gene, as a potentially key molecule that links ATRF, sympathetic vascular tone, and BP circadian rhythm. Collectively, these data reveal an important but previously unrecognized role of the timing of food intake in the onset, prevention, and treatment of nondipping BP in diabetes.

scholarly journals Time-restricted feeding regulates circadian rhythm of murine uterine clock

2021 ◽  
Author(s):  
Takashi Hosono ◽  
Masanori Ono ◽  
Takiko Daikoku ◽  
Michihiro Mieda ◽  
Satoshi Nomura ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Protein Expression ◽  
Western Blot ◽  
Active Phase ◽  
Active Period ◽  
Restricted Feeding ◽  
Group Iii ◽  
Breakfast Skipping ◽  
Group I

Abstract Background Skipping breakfast is associated with dysmenorrhea in young women. This suggests that the delay of food intake in the active phase impairs uterine functions by interfering with circadian rhythms. Objective To examine the relationship between the delay of feeding and uterine circadian rhythms, we investigated the effects of the first meal occasion in the active phase on the uterine clock. Methods Zeitgeber time (ZT) was defined as ZT 0 (8:45) with lights on and ZT 12 (20:45) with lights off. Young female mice (8 weeks of age) were divided into 3 groups: group I (ad-libitum feeding), group II (time-restricted feeding during ZT12–16, initial 4 hours of the active period), and group III (time-restricted feeding during ZT20–24, last 4 hours of the active period, a breakfast-skipping model). After two weeks of dietary restriction, mice in each group were sacrificed at 4-hour intervals and the expression profiles of uterine clock genes, Bmal1, Per1, Per2, and Cry1, were examined. Results qPCR and Western blot analyses demonstrated synchronized circadian clock gene expression within the uterus. Immunohistochemical analysis confirmed that Bmal1 protein expression was synchronized among the endometrium and myometrium. In groups I and II, mRNA expression of Bmal1 was elevated after ZT12 at the start of the active phase. In contrast, Bmal1 expression was elevated just after ZT20 in group III, showing that the uterine clock rhythm had shifted 8 hours backward. The changes in Bmal1 protein expression were confirmed by Western blot analysis. Conclusion This study is the first to indicate that time-restricted feeding regulates a circadian rhythm of the uterine clock that is synchronized throughout the uterine body. These findings suggest that the uterine clock system is a new candidate to explain the etiology of breakfast skipping-induced uterine dysfunction.

scholarly journals ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2020 ◽  
Author(s):  
Xiaobing Cui ◽  
Jia Fei ◽  
Sisi Chen ◽  
Gaylen L. Edwards ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
High Fat Diet ◽  
Peptide Yy ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Insulin Tolerance ◽  
Normal Chow

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1+/-) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Adar1+/- mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1+/- improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1+/- mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1+/- protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1+/- restored the increased ghrelin expression in stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induce obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion.

Viewing the ventromedial hypothalamus from the adrenal gland

1984 ◽  
Vol 246 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
M. F. Dallman
Keyword(s):  
Circadian Rhythm ◽  
Insulin Secretion ◽  
Food Intake ◽  
Adrenal Gland ◽  
Ventromedial Hypothalamus ◽  
Adrenocortical Function ◽  
Suprachiasmatic Nuclei ◽  
Inhibit Food Intake ◽  
Dose Dependent

The relationships among food intake, insulin secretion, and adrenocortical function are reviewed. It is hypothesized that a major role of structures in, or passing through, the ventromedial hypothalamus is to inhibit food intake, insulin secretion, and adrenocortical function during the day (in the nocturnally active rat) and that this activity is normally driven by elements within the suprachiasmatic nuclei. Lesions of the ventromedial hypothalamus of rats result in nonrhythmic food intake, hyperinsulinemia, nonrhythmic adrenocortical function, and obesity. Adrenalectomy prevents or reverses the effects of lesions of the ventromedial hypothalamus on food intake, insulin secretion, and obesity, and corticosteroid replacement restores them. Because the actions of corticosteroids are both time- and dose-dependent, it is proposed that the effects of the tonic levels of corticosteroids observed after lesions of the ventromedial hypothalamus are to augment the hyperphagia, hyperinsulinemia, and substrate flow into fat to a greater extent than would occur if there were a normal circadian rhythm in adrenocortical function.

N-methyl-d-aspartate receptor coagonist d-serine suppresses intake of high-preference food

2015 ◽  
Vol 309 (5) ◽  
pp. R561-R575 ◽  
Author(s):  
Tsutomu Sasaki ◽  
Yoshihiro Kinoshita ◽  
Sho Matsui ◽  
Shigeru Kakuta ◽  
Hiromi Yokota-Hashimoto ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Food Choice ◽  
Food Access ◽  
High Preference ◽  
Normal Chow ◽  
The One ◽  
Different Strains ◽  
Agouti Related Protein

d-Serine is abundant in the forebrain and physiologically important for modulating excitatory glutamatergic neurotransmission as a coagonist of synaptic N-methyl-d-aspartate (NMDA) receptor. NMDA signaling has been implicated in the control of food intake. However, the role of d-serine on appetite regulation is unknown. To clarify the effects of d-serine on appetite, we investigated the effect of oral d-serine ingestion on food intake in three different feeding paradigms (one-food access, two-food choice, and refeeding after 24-h fasting) using three different strains of male mice (C57Bl/6J, BKS, and ICR). The effect of d-serine was also tested in leptin signaling-deficient db/ db mice and sensory-deafferented (capsaicin-treated) mice. The expression of orexigenic neuropeptides [neuropeptide Y ( Npy) and agouti-related protein ( Agrp)] in the hypothalamus was compared in fast/refed experiments. Conditioned taste aversion for high-fat diet (HFD) was tested in the d-serine-treated mice. Under the one-food-access paradigm, some of the d-serine-treated mice showed starvation, but not when fed normal chow. HFD feeding with d-serine ingestion did not cause aversion. Under the two-food-choice paradigm, d-serine suppressed the intake of high-preference food but not normal chow. d-Serine also effectively suppressed HFD intake but not normal chow in db/ db mice and sensory-deafferented mice. In addition, d-serine suppressed normal chow intake after 24-h fasting despite higher orexigenic gene expression in the hypothalamus. d-Serine failed to suppress HFD intake in the presence of L-701,324, the selective and full antagonist at the glycine-binding site of the NMDA receptor. Therefore, d-serine suppresses the intake of high-preference food through coagonism toward NMDA receptors.

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 Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mario Caba ◽  
Enrique Meza ◽  
Carolina Escobar ◽  
Angeles Jiménez ◽  
Mario Daniel Caba-Flores ◽  
...  
Keyword(s):  
Food Intake ◽  
Hypothalamic Nucleus ◽  
Restricted Feeding ◽  
Adult Rats ◽  
Peripheral Oscillators ◽  
Food Anticipatory Activity ◽  
Ad Libitum ◽  
Anticipatory Activity ◽  
Oxytocinergic Cells

AbstractThe mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

scholarly journals Oxytocinergic Cells of the Posterior Hypothalamic Paraventricular Nucleus Participate in the Food Entrained Clock

2021 ◽  
Author(s):  
Mario Caba ◽  
Enrique Meza ◽  
Carolina Escobar ◽  
Angeles Jiménez ◽  
Mario Daniel Caba-Flores ◽  
...  
Keyword(s):  
Food Intake ◽  
Hypothalamic Nucleus ◽  
Restricted Feeding ◽  
Adult Rats ◽  
Peripheral Oscillators ◽  
Food Anticipatory Activity ◽  
Ad Libitum ◽  
Anticipatory Activity ◽  
Oxytocinergic Cells

Abstract The mechanisms underlying food anticipatory activity is still not well understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON) and in the medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), Ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or Ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; contrasting, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

scholarly journals Subfornical organ insulin receptors tonically modulate cardiovascular and metabolic function

2019 ◽  
Vol 51 (8) ◽  
pp. 333-341 ◽  
Author(s):  
Jin Kwon Jeong ◽  
Julie A. Horwath ◽  
Hayk Simonyan ◽  
Katherine A. Blackmore ◽  
Scott D. Butler ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Receptor ◽  
Insulin Receptors ◽  
Subfornical Organ ◽  
Chow Diet ◽  
Receptor Signaling ◽  
Arterial Blood ◽  
Adenoviral Delivery ◽  
Insulin Receptor Signaling ◽  
Normal Chow

Insulin acts within the central nervous system through the insulin receptor to influence both metabolic and cardiovascular physiology. While a major focus has been placed on hypothalamic regions, participation of extrahypothalamic insulin receptors in cardiometabolic regulation remains largely unknown. We hypothesized that insulin receptors in the subfornical organ (SFO), a forebrain circumventricular region devoid of a blood-brain barrier, are involved in metabolic and cardiovascular regulation. Immunohistochemistry in mice revealed widespread insulin receptor-positive cells throughout the rostral to caudal extent of the SFO. SFO-targeted adenoviral delivery of Cre-recombinase in insulin receptorlox/lox mice resulted in sufficient ablation of insulin receptors in the SFO. Interestingly, when mice were maintained on a normal chow diet, deletion of SFO insulin receptors resulted in greater weight gain and adiposity, relative to controls, independently of changes in food intake. In line with this, ablation of insulin receptors in the SFO was associated with marked hepatic steatosis and hypertriglyceridemia. Selective removal of SFO insulin receptors also resulted in a lower mean arterial blood pressure, which was primarily due to a reduction in diastolic blood pressure, whereas systolic blood pressure remained unchanged. Cre-mediated targeting of SFO insulin receptors did not influence heart rate. These data demonstrate multidirectional roles for insulin receptor signaling in the SFO, with ablation of SFO insulin receptors resulting in an overall deleterious metabolic state while at the same time maintaining blood pressure at low levels. These novel findings further suggest that alterations in insulin receptor signaling in the SFO could contribute to metabolic syndrome phenotypes.

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