A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

Mohr, Adélaïde A.; García-Serrano, Alba M.; Vieira, Joao P P; Skoug, Cecilia; Davidsson, Henrik; Duarte, João M. N.

doi:10.1177/0271678x20942397

Cited by 14 publications

(20 citation statements)

References 38 publications

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“…Other studies have shown before that the chronic consumption of high fat diets leads to obesity and negatively affects brain function in terms of a worsen outcome after ischemic stroke 41 and that short-term high-fat and high-sucrose feeding impairs hypothalamic neuronal circuits, particularly in the arcuate, the ventromedial and the dorsomedial nucleus. 42 Visa versa, short-term exercise training effectively decreases insulin-stimulated brain glucose uptake in sedentary subjects with insulin resistance. 43 Moreover, insulin-induced CBF reduction may be an important determinant of cognitive decline observed in obesity.…”

Section: Discussionmentioning

confidence: 99%

Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

Huber

Ogrodnik

Wenzel

et al. 2021

J Cereb Blood Flow Metab

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Angiotensin II receptor blockers (telmisartan) prevent rodents from diet-induced obesity and improve their metabolic status. Hyperglycemia and obesity are associated with reduced cerebral blood flow and neurovascular uncoupling which may lead to behavioral deficits. We wanted to know whether a treatment with telmisartan prevents these changes in obesity. We put young mice on high-fat diet and simultaneously treated them with telmisartan. At the end of treatment, we performed laser speckle imaging and magnetic resonance imaging to assess the effect on neurovascular coupling and cerebral blood flow. Different behavioral tests were used to investigate cognitive function. Mice developed diet-induced obesity and after 16, not 8 weeks of high-fat diet, however, the response to whisker pad stimulation was about 30% lower in obese compared to lean mice. Simultaneous telmisartan treatment increased the response again by 10% compared to obese mice. Moreover, telmisartan treatment normalized high-fat diet-induced reduction of cerebral blood flow and prevented a diet-induced anxiety-like behavior. In addition to that, telmisartan affects cellular senescence and string vessel formation in obesity. We conclude, that telmisartan protects against neurovascular unit impairments in a diet-induced obesity setting and may play a role in preventing obesity related cognitive deficits in Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

Huber

Ogrodnik

Wenzel

et al. 2021

J Cereb Blood Flow Metab

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“…Mice under isoflurane anesthesia were sacrificed by cardiac perfusion with cold PBS and then cold phosphate-buffered formaldehyde (Histolab, Askim, Sweden), and brains were cryosectioned into 20 µm slices [ 21 ]. Immunolabeling was carried out as detailed previously [ 23 ] with the primary antibodies: rabbit anti-allograft inflammatory factor 1 (Iba1, dilution 1:200; #019-19741, Fujifilm Wako, Japan; RRID:AB_839504), rat anti-CD11b (dilution 1:500; #MCA711, Bio-Rad, Sundbyberg, Sweden; RRID:AB_321292), anti-glial fibrillary acidic protein (GFAP) pre-tagged with AF488 (dilution 1:500; #53-9892-82, ThermoFisher Scientific, Göteborg, Sweden; RRID:AB_10598515), rabbit anti-glutamine synthetase (dilution 1:250; #ab176562, Abcam, Cambridge, UK; RRID:AB_2868472), anti-NeuN pre-tagged with AF488 (dilution 1:100; Cat# ab190195, Abcam; RRID:AB_2716282) and rabbit anti-doublecortin (dilution 1:500; #AB2253, Millipore-Merck, Darmstadt, Germany; RRID:AB_1586992). Secondary antibodies (dilution 1:500) were from ThermoFisher: AF568-conjugated goat anti-Rabbit IgG (#A-21069; RRID: AB_141416), AF568-conjugated goat anti-rat IgG (#A-21247; RRID:AB_141778) and AF488-conjugated goat anti-guinea-pig IgG (#A-11073; RRID:AB_2534117).…”

Section: Methodsmentioning

confidence: 99%

Cognitive Impairment and Metabolite Profile Alterations in the Hippocampus and Cortex of Male and Female Mice Exposed to a Fat and Sugar-Rich Diet are Normalized by Diet Reversal

García-Serrano¹,

Mohr²,

Philippe³

et al. 2022

Aging and disease

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Diabetes impacts on brain metabolism, structure, and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. However, it remains to be determined whether brain dysfunction induced by obesogenic diets results from permanent brain alterations. We tested the hypothesis that an obesogenic diet (high-fat and high-sucrose diet; HFHSD) causes reversible changes in hippocampus and cortex metabolism and alterations in behavior. Mice were exposed to HFHSD for 24 weeks or for 16 weeks followed by 8 weeks of diet normalization. Development of the metabolic syndrome, changes in behavior, and brain metabolite profiles by magnetic resonance spectroscopy (MRS) were assessed longitudinally. Control mice were fed an ingredient-matched low-fat and low-sugar diet. Mice fed the HFHSD developed obesity, glucose intolerance and insulin resistance, with a more severe phenotype in male than female mice. Relative to controls, both male and female HFHSD-fed mice showed increased anxiety-like behavior, impaired memory in object recognition tasks, but preserved working spatial memory as evaluated by spontaneous alternation in a Y-maze. Alterations in the metabolite profiles were observed both in the hippocampus and cortex but were more distinct in the hippocampus. HFHSD-induced metabolic changes included altered levels of lactate, glutamate, GABA, glutathione, taurine, N -acetylaspartate, total creatine and total choline. Notably, HFHSD-induced metabolic syndrome, anxiety, memory impairment, and brain metabolic alterations recovered upon diet normalization for 8 weeks. In conclusion, cortical and hippocampal derangements induced by long-term HFHSD consumption are reversible rather than being the result of permanent tissue damage.

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“…114 Finally, a very recent work described a robust experimental paradigm to assess real-time glucose-induced fMRI tasks in the mouse brain, and found that one-week high-fat and high-sucrose feeding impaired neuronal circuits in mice, particularly in the ARC, dorsomedial nucleus (DMN) and ventromedial nucleus + lateral hypothalamus (VMN+LH). 115…”

Section: Magnetic Resonance Imaging and Spectroscopy Of Cerebral Altementioning

confidence: 99%

Magnetic resonance assessment of the cerebral alterations associated with obesity development

Lizarbe

Campillo

Guadilla

et al. 2020

J Cereb Blood Flow Metab

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Obesity is a current threat to health care systems, affecting approximately 13% of the world’s adult population, and over 18% children and adolescents. The rise of obesity is fuelled by inadequate life style habits, as consumption of diets rich in fats and sugars which promote, additionally, the development of associated comorbidities. Obesity results from a neuroendocrine imbalance in the cerebral mechanisms controlling food intake and energy expenditure, including the hypothalamus and the reward and motivational centres. Specifically, high-fat diets are known to trigger an early inflammatory response in the hypothalamus that precedes weight gain, is time-dependent, and eventually extends to the remaining appetite regulating regions in the brain. Multiple magnetic resonance imaging (MRI) and spectroscopy (MRS) methods are currently available to characterize different features of cerebral obesity, including diffusion weighted, T2 and volumetric imaging and 1H and 13C spectroscopic evaluations. In particular, consistent evidences have revealed increased water diffusivity and T2 values, decreased grey matter volumes, and altered metabolic profiles and fluxes, in the brain of animal models and in obese humans. This review provides an integrative interpretation of the physio-pathological processes associated with obesity development in the brain, and the MRI and MRS methods implemented to characterize them.

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A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

Cited by 14 publications

References 38 publications

Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

Cognitive Impairment and Metabolite Profile Alterations in the Hippocampus and Cortex of Male and Female Mice Exposed to a Fat and Sugar-Rich Diet are Normalized by Diet Reversal

Magnetic resonance assessment of the cerebral alterations associated with obesity development

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