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Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat.

ABSTRACT: Body weight is regulated by interoceptive neural circuits that track energy need, but how the activity of these circuits is altered in obesity remains poorly understood. Here we describe the in vivo dynamics of hunger-promoting AgRP neurons during the development of diet-induced obesity in mice. We show that high-fat diet attenuates the response of AgRP neurons to an array of nutritionally-relevant stimuli including food cues, intragastric nutrients, cholecystokinin and ghrelin. These alterations are specific to dietary fat but not carbohydrate or protein. Subsequent weight loss restores the responsiveness of AgRP neurons to exterosensory cues but fails to rescue their sensitivity to gastrointestinal hormones or nutrients. These findings reveal that obesity triggers broad dysregulation of hypothalamic hunger neurons that is incompletely reversed by weight loss and may contribute to the difficulty of maintaining a reduced weight.

SUBMITTER: Beutler LR

PROVIDER: S-EPMC7398661 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat.

Beutler Lisa R LR Corpuz Timothy V TV Ahn Jamie S JS Kosar Seher S Song Weimin W Chen Yiming Y Knight Zachary A ZA

eLife 20200728

Body weight is regulated by interoceptive neural circuits that track energy need, but how the activity of these circuits is altered in obesity remains poorly understood. Here we describe the in vivo dynamics of hunger-promoting AgRP neurons during the development of diet-induced obesity in mice. We show that high-fat diet attenuates the response of AgRP neurons to an array of nutritionally-relevant stimuli including food cues, intragastric nutrients, cholecystokinin and ghrelin. These alteration ...[more]

PMID: 32720646

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Project description:BackgroundObesity is a risk factor for chronic kidney disease (CKD). While the exact mechanisms remain unclear, inflammation may be a consequence of obesity that directly impacts the kidneys. The aim of this study was to examine the inflammatory status of the kidneys and potential ongoing renal damage, i.e., tubular damage and fibrosis after long-term obesity maintained through persistent consumption of a high-fat diet (HFD).ResultsTwenty-four-week-old male Long-Evans (LEV) rats were continuously fed a control diet (CD) or HFD for 51?weeks. The mean body weight was higher in HFD-fed rats than in control diet-fed rats and markedly elevated during the last 24?weeks. Blood analyses revealed no substantial alterations in renal functional parameters by HFD consumption but a substantial increase in creatine kinase, a muscle loss marker. Magnetic resonance imaging (MRI) was utilized to quantify rat quadriceps muscle mass. The data showed that HFD-induced obesity in LEV rats was accompanied by minor decreases in muscle mass and strength at 75?weeks of age. Rat kidney inflammatory status was evaluated using histological and immunohistological techniques. The number of foci with immune cell infiltrates and infiltrating monocytes/macrophages was significantly increased in HFD-fed rat kidneys at week 75. Renal fibrosis parameters, including glomerulosclerosis and tubular damage, were also markedly increased in renal tissues from HFD-fed rats compared to the controls. The significant increase in tubular protein casts in HFD-fed rat tissues indicated that renal function was already disturbed. Rat kidney inflammatory status was further evaluated using the simultaneous profiling of twenty-two inflammatory markers in kidney tissue extracts. Consistently, MCP-1 and eotaxin (CCL11) levels were elevated in obese LEV rat kidneys.ConclusionsCompared to CD-fed rats, HFD-fed obese LEV rats show significant damage of renal structures with aging. These subtle changes may sensitize the kidneys to the development of progressive CKD.

Dataset Information

Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat.

Publications

Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat.

Similar Datasets

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