The latest paper from Sichuan University: For the first time, the central mechanism of the new factor MANF through POMC neurons regulating the energy balance of the system is revealed

In November 2022, the team of Professor He Jinhan of the Institute of Metabolic Diseases and Therapeutics of our hospital published a research paper entitled "MANF in POMC neurons promotes brown adipose tissue thermogenesis and protects against diet-induced obesity" in the well-known international journal in the field of diabetes.
For the first time, the important regulatory role of MENM, astrocyte-derived neurotrophic factor MANF on the energy balance of the body in hypothalamic POMC neurons was revealed, and the central and peripheral molecular mechanisms
of its regulation of system energy metabolism through the "dialogue" of hypothalamus-adipose tissue were clarified.
This study further confirms that MANF is a potential therapeutic target for obesity and related metabolic disorders, and provides a mechanistic basis for
its action.

The first author of this paper is Tang Qin, a full-time postdoctoral fellow at the Institute of Metabolic Diseases and Therapeutics, and the corresponding author is Professor
He Jinhan, Department of Pharmacy/Institute of Metabolic Diseases and Therapeutics.
The research work was supported
by the National Natural Science Foundation of China and the Sichuan Science and Technology Program.

Obesity is an important cause of chronic metabolic diseases such as cardiovascular disease and diabetes, and its root cause is the imbalance
between energy intake and consumption.
The mechanisms involved in the regulation of energy balance are complex, and the central nervous system plays a key role
in this process.
This study found that MANF was highly expressed in mouse hypothalamic POMC neurons, and diet-induced significantly decreased
expression levels of MANF in hypothalamic POMC neurons in obese mice.
Based on this, this study focuses on POMC neurons, one of the key neurons that regulate the energy balance of the system, and uses a variety of mouse models and molecular biological methods to systematically explain
the function and mechanism of MANF regulation system energy homeostasis in hypothalamic POMC neurons.
The results showed that POMC neuron-specific knockout MANF aggravated diet-induced weight gain and fat deposition in mice, and promoted glycolipid metabolism disorders.
However, hypothalamic POMC neuron-specific overexpression of MANF significantly improved diet-induced obesity and glucose metabolism disorders
.
Mechanistic studies have found that the loss of MANF in hypothalamic POMC neurons induces endoplasmic reticulum stress and leptin resistance, and further inhibits the thermogenic function of brown adipose tissue and reduces energy consumption by reducing the distribution and activity of sympathetic nerves in adipose tissue.
In contrast, MANF overexpression significantly improved endoplasmic reticulum homeostasis, increased sympathetic activity in adipose tissue and promoted energy expenditure
.
The study also found that MANF in hypothalamic POMC neurons had no significant effect
on the feeding behavior of mice.
This study provides a theoretical basis
for further understanding of the mechanism of action of MANF.

Figure 1.
Hypothalamic POMC neuron-specific knockout MANF promotes diet-induced obesity and fat deposition

Figure 2.
Specific overexpression of MANF by hypothalamic POMC neurons improves diet-induced obesity

Original link:

  https://diabetesjournals.
org/diabetes/article/71/11/2344/147413/MANF-in-POMC-Neurons-Promotes-Brown-Adipose-Tissue