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Glucose intolerance induces anxiety-like behaviors independent of obesity and insulin resistance in a novel model of nutritional metabolic stress.

Authors :
Al-Onaizi, Mohammed
Braysh, Kawthar
Alkafeef, Selma S.
Altarrah, Dana
Dannoon, Shorouk
Alasousi, Dalal
Adel, Hawraa
Al-Ajmi, Mariam
Kandari, Anwar
Najem, Rawan
Nizam, Rasheeba
Williams, Michayla R.
John, Sumi
Thanaraj, Thangavel Alphonse
Ahmad, Rasheed
Al-Hussaini, Heba
Al-Mulla, Fahd
Alzaid, Fawaz
Source :
Nutritional Neuroscience. Oct2024, Vol. 27 Issue 10, p1143-1161. 19p.
Publication Year :
2024

Abstract

Objectives: Type 2 diabetes (T2D) is a metabolic disease of major public health concern. It impacts peripheral tissues and the central nervous system, leading to systemic dysmetabolism and neurocognitive impairments, including memory deficits, anxiety, and depression. The metabolic determinants of these neurocognitive impairments remain unidentified. Here, we sought to address this question by developing a proprietary (P-) high-fat diet (HFD), in which glucose intolerance precedes weight gain and insulin resistance. Methods: The P-HFD model was nutritionally characterized, and tested in vivo in mice that underwent behavioral and metabolic testing. The diet was benchmarked against reference models.. Results: P-HFD has 42% kcal from fat, high monounsaturated/polyunsaturated fatty acid ratio, and 10% (w/v) sucrose in drinking water. When administered, from the early stages of glucose intolerance alone, animals exhibit anxiety-like behavior, without depression nor recognition memory deficits. Long-term P-HFD feeding leads to weight gain, brain glucose hypometabolism as well as impaired recognition memory. Using an established genetic model of T2D (db/db) and of diet-induced obesity (60% kcal from fat) we show that additional insulin resistance and obesity are associated with depressive-like behaviors and recognition memory deficits. Discussion: Our findings demonstrate that glucose intolerance alone can elicit anxiety-like behavior. Through this study, we also provide a novel nutritional model (P-HFD) to characterize the discrete effects of glucose intolerance on cognition, behavior, and the physiology of metabolic disease. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1028415X
Volume :
27
Issue :
10
Database :
Academic Search Index
Journal :
Nutritional Neuroscience
Publication Type :
Academic Journal
Accession number :
179995762
Full Text :
https://doi.org/10.1080/1028415X.2024.2310419