No abstract

The mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin signaling, respectively. Level of phosphoinositide-3-kinase (PI3K) after induction of beige adipocytes under conditions of normal insulin signaling, phosphorylated protein kinase B (pAKT), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), zinc-fifinger transcriptional factor PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPβ) were significantly increased. Conversely, when insulin signaling is incompletely inhibited, the expression of the thermogenic and adipogenic factors is significantly reduced, with obvious impairment of adipogenesis. However, phosphorylation level of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and expression level of sirtuin type 1 (SIRT1) had increased. These white preadipocytes from different donors showed similar dynamic change in morphology and molecular levels during the browning. The present data indicate that insulin signaling plays a important role in regulation of browning of hsASCs and msASCs through PI3K-AKT-UCP1 signaling pathway. The insulin-AMPK-SIRT1 pathway was also involved in the adipocytes browning, while its effect is limited.

(1) Background: Ectopic fat deposition and its effects, metabolic syndrome, have been significantly correlated to lifestyle and caloric consumption. There is no specific noninvasive evaluation tool being used in order to establish clinical markers for tracing the metabolic pathway implicated in obesity-related abnormalities that occur in the body as a result of a high-fat diet (HFD). The purpose of this work is to investigate in vivo ectopic fat distribution and in vitro metabolite profiles given by HFDs, as well as how they are inter-related, in order to find surrogate metabolic biomarkers in the development of metabolic syndrome utilizing noninvasive approaches. (2) Methods: Male Wistar rats were divided into a standard normal chow diet, ND group, and HFD group. After 16 weeks of different diet administration, blood samples were collected for proton nuclear magnetic resonance (1H NMR) and biochemical analysis. Magnetic resonance imaging/proton magnetic resonance spectroscopy (MRI/1H MRS) was performed on the abdomen, liver, and psoas muscle of the rats. (3) Results: Visceral fat showed the strongest relationship with blood cholesterol. Although liver fat content (LFC) was not associated with any biophysical profiles, it had the highest correlation with metabolites such as (-CH2)n very-low-density lipoprotein/low-density lipoprotein (VLDL/LDL), lactate, and N-acetyl glycoprotein of serum 1H NMR. HFD showed no obvious influence on muscle fat accumulation. Acetoacetate, N-acetyl glycoprotein, lactate, (-CH2)n VLDL/LDL, and valine were the five possible metabolic biomarkers used to differentiate HFD from ND in the present study. (4) Conclusions: Our study has validated the influence of long-term HFD-induced ectopic fat on body metabolism as well as the metabolic profile deterioration both in vivo and in vitro.