Optical Metabolic Imaging Uncovers Sex- and Diet-dependent Lipid Changes in Aging Drosophila Brain

Abstract

Aging is associated with progressive declines in physiological integrity and functions alongside increases in vulnerability to develop a number of diseases. The brain regulates sensory and motor functions as well as endocrine functions, and age-associated changes in brain are likely prerequisite for the organismal aging. Lipid metabolism has been associated with brain aging, which could be easily intervened by diets and lifestyles. However, the underlying mechanism through which brain lipid metabolism is regulated by diet during aging is elusive. Using stimulated Raman scattering (SRS) imaging combined with deuterium water (D2O) labeling, we visualized that lipid metabolic activities were changed by diet manipulation in aging Drosophila brain. Furthermore, we illuminated that insulin/IGF-1 signaling (IIS) pathway mediates the transformation of brain lipid metabolic changes in both an aging- and a diet-dependent manner. The lipid droplets (LDs) in the brain gradually became inert in both activities of lipid synthesis and mobilization with aging. High sugar diets enhanced the metabolic activity through promoting lipogenesis while dietary restriction increased the metabolic activity in both lipogenesis and lipolysis in brain LDs. However, these effects were impaired in both chico1/+ and dfoxo Drosophila mutants. We also observed that old chico1/+ brains maintained high metabolic activities, whilst the aged dfoxo brains acted exactly the opposite. More interestingly, the sexual dimorphism in brain lipid metabolism was impaired under diet regulation in both chico1/+ and dfoxo mutants. Locally reduced IIS activity in glial cells can mimic the systemic changes in systematic IIS mutants to maintain lipogenesis and lipolysis in aged brains, providing mechanistic insight into the anti-aging effects of IIS pathway. Our results highlight the manipulation of glia-specific IIS activity as a promising strategy in anti-aging treatments.

Subcellular resolution DO-SRS and 2PEF imaging of metabolic dynamics regulated by L-methionine in amyotrophic lateral sclerosis

“…Raman spectro-microscopy has been employed for molecular imaging with advantages including noninvasive, high subcellular resolution, and high chemical specificity [10][11]. Our lab further developed a novel, non-invasive multimodal imaging platform, combining heavy water (D2O) probed stimulated Raman scattering (DO-SRS) microscopy and two photon excitation fluorescence (2PEF) microscopy, to investigate the metabolism of a variety of biomolecules in cells and living organisms [12][13][14][15][16][17]. Deuterium ions of D2O can be harnessed and integrated into newly synthesized macromolecules via a series of enzymatic reactions to form C-D bonds (Figure 2A, B).…”

Effect of Resistance Training on Adipose Tissue and Serum METRNL Levels in Sucrose Solution Fed Rats

“…IR is caused by the intersection of multiple factors, including diet and a sedentary lifestyle (2). It is also stated that high-sugar diets play an axial role in metabolic dysregulation, leading to diseases including IR (3). Improving IR remains an important area of research in treating T2D and metabolic syndrome due to the need for new insulin-sensitizing therapies (4).…”