Friend or foe for obesity: How hepatokines remodel adipose tissues and translational perspective

Zhang, Yao; Wang, Yibing

doi:10.1016/j.gendis.2021.12.011

Cited by 2 publications

(3 citation statements)

References 232 publications

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“…Clinically, obesity is demarcated by a body mass index (BMI) exceeding 30 kg/m 2 , but this metric belies the complex, heterogeneous nature of the condition. The pathogenesis of obesity is a multifaceted interplay between genetic predisposition, epigenetic modifications, metabolic programming, and environmental factors, including diet, physical activity, and even microbial flora of the gut [9,12]. At the cellular level, obesity is the consequence of adipocyte hypertrophy and hyperplasia precipitated by chronic energy surplus.…”

Section: Obesity: An Epidemic Of Excessive Weight Gainmentioning

confidence: 99%

“…Moreover, obesity's pathophysiological impact extends beyond mere energy storage. Adipose tissue, particularly in visceral deposits, operates as an active endocrine organ, orchestrating a myriad of pathological processes through the dysregulated secretion of adipokines, pro-inflammatory cytokines, and non-esterified fatty acids [8,9]. These adipocyte-derived factors cause systemic insulin resistance, a cornerstone of metabolic syndrome, and incite a chronic, low-grade inflammatory state, which is implicated in the pathogenesis of a spectrum of non-communicable diseases [12].…”

Section: Obesity: An Epidemic Of Excessive Weight Gainmentioning

confidence: 99%

“…These molecules have systemic effects that influence insulin sensitivity, energy metabolism, inflammatory pathways, and liver function. The consequence is a self-perpetuating cycle of metabolic dysfunction that exacerbates the risk of further health complications [9].…”

Section: Introductionmentioning

confidence: 99%

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Dietary Determinants of Metabolic Syndrome: Focus on the Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Kumar Verma,

Tripathi,

Kumar Singh

2024

Metabolic Syndrome - Lifestyle and Biological Risk Factors [Working Title]

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Metabolic syndrome, a cluster of conditions including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels, significantly heightens the risk of cardiovascular disease, diabetes, obesity, and fatty liver disease. With the adoption of a Western-style diet characterized by a high intake of corn sugar, saturated fats, and ultra-processed foods, these metabolic disorders have reached pandemic proportions globally. This chapter addresses the rising rates of obesity and MASLD, stressing the critical impact of dietary habits on these issues. It highlights how a healthy diet can mitigate risks, pointing out the detrimental effects of poor nutrition. The text examines the complex relationship between diet, adiposity, and liver health, analyzing the role of macronutrient composition, calorie intake, and processed foods in metabolic dysregulation. It proposes comprehensive nutritional strategies and public health policies, including the adoption of an inverted food pyramid, to tackle metabolic syndrome, obesity, and MASLD effectively, advocating for a holistic approach to dietary changes.

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Section: Obesity: An Epidemic Of Excessive Weight Gainmentioning

confidence: 99%

Section: Obesity: An Epidemic Of Excessive Weight Gainmentioning

confidence: 99%

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Dietary Determinants of Metabolic Syndrome: Focus on the Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Kumar Verma,

Tripathi,

Kumar Singh

2024

Metabolic Syndrome - Lifestyle and Biological Risk Factors [Working Title]

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Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier

Fritzen,

Wienken,

Wagner

et al. 2024

Fluids Barriers CNS

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Background The most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet. Here, the truncated mini low-density lipoprotein receptor-related protein 1 mLRP1_DIV* was presented as blood to brain transport carrier, exemplified by antibodies and immunoliposomes using a systematic approach to screen the receptor and its ligands’ route across endothelial cells in vitro. Methods The use of mLRP1_DIV* as liposomal carrier into the CNS was validated based on internalization and transport assays across an in vitro model of the BBB using hcMEC/D3 and bEnd.3 cells. Trafficking routes of mLRP1_DIV* and corresponding cargo across endothelial cells were analyzed using immunofluorescence. Modulation of γ-secretase activity by immunoliposomes loaded with the γ-secretase modulator BB25 was investigated in co-cultures of bEnd.3 mLRP1_DIV* cells and CHO cells overexpressing human amyloid precursor protein (APP) and presenilin 1 (PSEN1). Results We showed that while expressed in vitro, mLRP1_DIV* transports both, antibodies and functionalized immunoliposomes from luminal to basolateral side across an in vitro model of the BBB, followed by their mLRP1_DIV* dependent release of the cargo. Importantly, functionalized liposomes loaded with the γ-secretase modulator BB25 were demonstrated to effectively reduce toxic Aß42 peptide levels after mLRP1_DIV* mediated transport across a co-cultured endothelial monolayer. Conclusion Together, the data strongly suggest mLRP1_DIV* as a promising tool for drug delivery into the CNS, as it allows a straight transport of cargo from luminal to abluminal side across an endothelial monolayer and it’s release into brain parenchyma in vitro, where it exhibits its intended therapeutic effect.

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Friend or foe for obesity: How hepatokines remodel adipose tissues and translational perspective

Cited by 2 publications

References 232 publications

Dietary Determinants of Metabolic Syndrome: Focus on the Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Dietary Determinants of Metabolic Syndrome: Focus on the Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier

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