Corrigendum: Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control

Circulating ghrelin is decreased in obesity, and peripheral ghrelin does not induce food intake in obese mice. We investigated whether ghrelin resistance was a centrally mediated phenomenon involving dysregulated neuropeptide Y (NPY) and agouti-related peptide (AgRP) circuits. We show that diet-induced obesity (DIO) (12 wk) suppresses the neuroendocrine ghrelin system by decreasing acylated and total plasma ghrelin, decreasing ghrelin and Goat mRNA in the stomach, and decreasing expression of hypothalamic GHSR. Peripheral (ip) or central (intracerebroventricular) ghrelin injection was able to induce food intake and arcuate nucleus Fos immunoreactivity in chow-fed but not high-fat diet-fed mice. DIO decreased expression of Npy and Agrp mRNA, and central ghrelin was unable to promote expression of these genes. Ghrelin did not induce AgRP or NPY secretion in hypothalamic explants from DIO mice. Injection of NPY intracerebroventricularly increased food intake in both chow-fed and high-fat diet-fed mice, indicating that downstream NPY/AgRP neural targets are intact and that defective NPY/AgRP function is a primary cause of ghrelin resistance. Ghrelin resistance in DIO is not confined to the NPY/AgRP neurons, because ghrelin did not stimulate growth hormone secretion in DIO mice. Collectively, our data suggests that DIO causes ghrelin resistance by reducing NPY/AgRP responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis to limit further food intake. Ghrelin has a number of functions in the brain aside from appetite control, including cognitive function, mood regulation, and protecting against neurodegenerative diseases. Thus, central ghrelin resistance may potentiate obesity-related cognitive decline, and restoring ghrelin sensitivity may provide therapeutic outcomes for maintaining healthy aging.

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Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control

Frontiers in Endocrinology ◽

10.3389/fendo.2021.727915 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongxiao Zhang ◽

Satoshi Yamaguchi ◽

Xinhao Zhang ◽

Boxuan Yang ◽

Naoko Kurooka ◽

...

Keyword(s):

Food Intake ◽

Target Gene ◽

Potential Candidate ◽

Appetite Control ◽

Diet Induced Obesity ◽

Obesity And Diabetes ◽

Hypothalamic Arcuate Nucleus ◽

High Sucrose ◽

Major Target

In obesity and type 2 diabetes, numerous genes are differentially expressed, and microRNAs are involved in transcriptional regulation of target mRNAs, but miRNAs critically involved in the appetite control are not known. Here, we identified upregulation of miR-342-3p and its host gene Evl in brain and adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir342 (-/-) mice fed with HFHS chow were protected from obesity and diabetes. The hypothalamic arcuate nucleus neurons co-express Mir342 and EVL. The percentage of activated NPY+pSTAT3+ neurons were reduced, while POMC+pSTAT3+ neurons increased in Mir342 (-/-) mice, and they demonstrated the reduction of food intake and amelioration of metabolic phenotypes. Snap25 was identified as a major target gene of miR-342-3p and the reduced expression of Snap25 may link to functional impairment hypothalamic neurons and excess of food intake. The inhibition of miR-342-3p may be a potential candidate for miRNA-based therapy.

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Corrigendum: Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control

Frontiers in Endocrinology ◽

10.3389/fendo.2021.811189 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongxiao Zhang ◽

Satoshi Yamaguchi ◽

Xinhao Zhang ◽

Boxuan Yang ◽

Naoko Kurooka ◽

...

Keyword(s):

Appetite Control ◽

Diet Induced Obesity

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Trefoil Factor Family Member 2 Expression as an Indicator of the Severity of the High-Fat Diet-Induced Obesity

Genes ◽

10.3390/genes12101505 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1505

Author(s):

Abdelaziz Ghanemi ◽

Mayumi Yoshioka ◽

Jonny St-Amand

Keyword(s):

Family Member ◽

High Fat Diet ◽

Negative Energy ◽

Trefoil Factor ◽

High Fat ◽

Appetite Control ◽

Specific Expression ◽

Knock Out ◽

Diet Induced Obesity ◽

Trefoil Factor Family

Trefoil Factor Family Member 2 (TFF2) belongs to TFF family peptides that includes TFF1, TFF2, TFF3. TFF2 is mainly known for its roles in the mucosal protection. In the context of obesity and high fat diet (HFD), Tff2 has been characterized as a HFD-induced gene. The knock-out of Tff2 in mice lead to the protection from HFD-induced obesity with a metabolic profile towards a negative energy balance. Such HFD-specific expression gives Tff2 a pattern worth exploring in biomedical research. Indeed, measuring TFF2/TFF2/Tff2 expression in biological samples following the ingestion of high-fat diet reflects the biological “responsiveness” to the lipids ingestion and would reflect the severity of obesity establishment afterwards. Such property could be explored for instance to screen animal models, evaluate the predisposition to HFD-induced obesity as well as in biomedical and clinical applications. Results might advance obesity research especially in terms of understanding lipid-induced signals, appetite control and adiposity storage.

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