Role of the Gut Microbiome in Beta Cell and Adipose Tissue Crosstalk: A Review

Abstract

In the last decades, obesity has reached epidemic proportions worldwide. Obesity is a chronic disease associated with a wide range of comorbidities, including insulin resistance and type 2 diabetes mellitus (T2D), which results in significant burden of disease and major consequences on health care systems. Of note, intricate interactions, including different signaling pathways, are necessary for the establishment and progression of these two closely related conditions. Altered cell-to-cell communication among the different players implicated in this equation leads to the perpetuation of a vicious circle associated with an increased risk for the development of obesity-related complications, such as T2D, which in turn contributes to the development of cardiovascular disease. In this regard, the dialogue between the adipocyte and pancreatic beta cells has been extensively studied, although some connections are yet to be fully elucidated. In this review, we explore the potential pathological mechanisms linking adipocyte dysfunction and pancreatic beta cell impairment/insulin resistance. In addition, we evaluate the role of emerging actors, such as the gut microbiome, in this complex crosstalk.

Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications

“…Studies have shown that the occurrence of insulin resistance is closely related to gut microbiota disorder (Martinez-Montoro et al, 2022). Zeng et al compared the gut microbiota of PCOS patients with insulin resistance with that of the healthy control group, and found that the abundance of Prevotella decreased and Bacteroides increased in the former group (Zeng et al, 2019).…”

Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes

“…Moreover, NOD1 and NOD2, members of the NOD-like receptor (NLR) family, are present in both adipocytes and immune cells within adipose tissue and play significant roles in adipose tissue dysfunction. Activation of NOD1 is associated with insulin resistance, whereas NOD2 null mice develop chronic inflammation and insulin resistance without change in adiposity upon being fed an HFD (Denou et al, 2015;Chan et al, 2017;Martínez-Montoro et al, 2022). Overall, these pattern recognition receptors contribute to adipose tissue inflammation, metabolic dysregulation, and impaired insulin sensitivity.…”

“…Elevated FFAs inhibit glucosestimulated insulin secretion and lead to β-cell dysfunction through cytotoxic mechanisms, including apoptosis. FFAs exposure is associated with ceramide synthesis, mitochondrial dysfunction, overexpression of apoptotic genes, and intracellular triglyceride accumulation in β-cells mediated by sterol regulatory element-binding proteins (SREBPs) (Martínez-Montoro et al, 2022). Visceral adipose tissue releases proinflammatory factors like IL-2, IL-6, IL-8, IL-12A, and MCP-1 in obese conditions, which can contribute to β-cell dysfunction.…”

Thirty Obesity Myths, Misunderstandings, and/or Oversimplifications: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022

“…Gram positive Firmicutes may more efficiently extract calories from carbohydrates (via fermentation) than Gram negative Bacteroidetes [ 143 ]. Intestinal bacteria may also affect energy balance via central nervous system [ 144 ] and other body organ signaling, including crosstalk with adipose tissue [ 145 ]. Intestinal bacteria can also affect bile acid metabolism and gut hormone secretion; both which affect energy balance [ 9 ].…”