Editors
3
Impact
Loading...
Review
27 May 2021
Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis
Andrew Folick
1 more and 
Martin Valdearcos
Article Cover Image

In mammals, myeloid cells help maintain the homeostasis of peripheral metabolic tissues, and their immunologic dysregulation contributes to the progression of obesity and associated metabolic disease. There is accumulating evidence that innate immune cells also serve as functional regulators within the mediobasal hypothalamus (MBH), a critical brain region controlling both energy and glucose homeostasis. Specifically, microglia, the resident parenchymal myeloid cells of the CNS, play important roles in brain physiology and pathology. Recent studies have revealed an expanding array of microglial functions beyond their established roles as immune sentinels, including roles in brain development, circuit refinement, and synaptic organization. We showed that microglia modulate MBH function by transmitting information resulting from excess nutrient consumption. For instance, microglia can sense the excessive consumption of saturated fats and instruct neurons within the MBH accordingly, leading to responsive alterations in energy balance. Interestingly, the recent emergence of high-resolution single-cell techniques has enabled specific microglial populations and phenotypes to be profiled in unprecedented detail. Such techniques have highlighted specific subsets of microglia notable for their capacity to regulate the expression of lipid metabolic genes, including lipoprotein lipase (LPL), apolipoprotein E (APOE) and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2). The discovery of this transcriptional signature highlights microglial lipid metabolism as a determinant of brain health and disease pathogenesis, with intriguing implications for the treatment of brain disorders and potentially metabolic disease. Here we review our current understanding of how changes in microglial lipid metabolism could influence the hypothalamic control of systemic metabolism.

9,105 views
28 citations
11,935 views
6 citations
Review
18 March 2021
Astrocyte Clocks and Glucose Homeostasis
Olga Barca-Mayo
 and 
Miguel López

The endogenous timekeeping system evolved to anticipate the time of the day through the 24 hours cycle of the Earth’s rotation. In mammals, the circadian clock governs rhythmic physiological and behavioral processes, including the daily oscillation in glucose metabolism, food intake, energy expenditure, and whole-body insulin sensitivity. The results from a series of studies have demonstrated that environmental or genetic alterations of the circadian cycle in humans and rodents are strongly associated with metabolic diseases such as obesity and type 2 diabetes. Emerging evidence suggests that astrocyte clocks have a crucial role in regulating molecular, physiological, and behavioral circadian rhythms such as glucose metabolism and insulin sensitivity. Given the concurrent high prevalence of type 2 diabetes and circadian disruption, understanding the mechanisms underlying glucose homeostasis regulation by the circadian clock and its dysregulation may improve glycemic control. In this review, we summarize the current knowledge on the tight interconnection between the timekeeping system, glucose homeostasis, and insulin sensitivity. We focus specifically on the involvement of astrocyte clocks, at the organism, cellular, and molecular levels, in the regulation of glucose metabolism.

7,321 views
14 citations
Open for submission
Frontiers Logo

Frontiers in Endocrinology

The Need for an Integrative Approach in Type 1 Diabetes Management
Edited by Bettina Berger, David D. Martin
Deadline
06 May 2025
Submit a paper
Recommended Research Topics
Frontiers Logo

Frontiers in Endocrinology

Molecular Mechanism of Neuronal Dysfunction in the Diabetic Brain
Edited by Subbiah Pugazhenthi, Marc Lee Goalstone
54.6K
views
30
authors
7
articles
Frontiers Logo

Frontiers in Endocrinology

The Changing Panorama of Diabetes Outcomes: Novel Complications and Novelties in Classical Complication
Edited by Khalid Siddiqui, Ernesto Maddaloni
82.5K
views
58
authors
9
articles
Frontiers Logo

Frontiers in Endocrinology

Heterogeneity of Clinical Phenotypes in Type 1 Diabetes and of Beta Cell Deterioration in Type 1 Diabetes
Edited by Xia Li, Zhenqi Liu, Mei Zhang, Jinhua Yan
34.1K
views
54
authors
8
articles
Frontiers Logo

Frontiers in Endocrinology

Metabolic Miscommunication Among Organs: The Missing Links
Edited by Maria Paula Macedo, Maria João Meneses, SONIA MICHAEL NAJJAR, Ruben Nogueiras
56.3K
views
77
authors
12
articles
Frontiers Logo

Frontiers in Endocrinology

Deciphering the immunological and neuronal regulators of diabesity
Edited by CHANDAN SONA, Mainak Banerjee, Surendra Ugale
Deadline
20 Mar 2024
Submit