A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects

Liang, Hanyu; Lum, Helen; Alvarez, A. Villanueva; Garduño-García, José de Jesús; Daniel, Benjamin J.; Musi, Nicolas

doi:10.1371/journal.pone.0195810

Cited by 28 publications

(26 citation statements)

References 35 publications

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“…During obesity, the pro-inflammatory cytokines IL-1β and TNF-α can interfere directly with insulin signaling in adipocytes (Liang et al, 2018). We observed that IL-1β expression in the OBF group did not differ from C and OB groups, while TNF-α levels were similar between all groups (C, OB, OBF and OBP) (Fig.…”

Section: Discussionmentioning

confidence: 68%

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

Marchesin

Celiberto

Orlando

et al. 2018

Journal of Functional Foods

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A B S T R A C TThis work investigates the effect of a soy-based probiotic drink (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) on the fecal microbiota composition, body weight and inflammatory parameters in diet-induced obese mice. The probiotic group had a lower body weight until 9th week of the study, reduced area and diameter of adipocytes, and showed a significant increase of IL-6 and IL-10 compared to the obesite non-treated group. The intake of a high-fat diet results in an increase of Lactobacillus spp. while the probiotic drink positively modulates the intestinal microbiota by maintaining the population of microorganisms belonging to the phylum Bacteroidetes and increases Bifidobacterium spp. Our study finds that the regular intake of this probiotic drink is able to reduce body weight gain and the size of adipocytes while modulating the fecal microbiota and the immune profile of animals, therefore acting in a beneficial manner in the control of obesity.

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Section: Discussionmentioning

confidence: 68%

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

Marchesin

Celiberto

Orlando

et al. 2018

Journal of Functional Foods

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“…According to the literature,20 insulin secretion is a complex process with various influencing factors, and FFA metabolism may exert double-sided effects on this course. FFA, at relatively low levels, functions as an energy source to provide ATP.…”

Section: Discussionmentioning

confidence: 99%

Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people

Xin¹,

Wang²,

Chi³

et al. 2019

DMSO

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BackgroundFree fatty acids (FFAs) are associated with insulin secretion and insulin resistance. However, the associations among FFAs, obesity, and progression from a normal to a prediabetic state are unclear.MethodsNondiabetic subjects (5,952) were divided in two groups according to their body mass index (BMI): obese subjects (BMI ≥24 kg/m2) and nonobese subjects (BMI <24 kg/m2). Clinical and multiple glucolipid metabolism data were collected. The homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) was used. HbA1c level between 5.7% and 6.4% was considered prediabetic. Nonparametric tests, one-way ANOVA, and linear correlation analysis were performed. R and SPSS 23.0 software programs were used to analyze the results.ResultsA U-shaped relationship between FFAs and HOMA-IR was observed. After adjusting for potential confounders, the turning points of FFA levels in the curves were 0.54 mmol/L in the nonobese group and 0.61 mmol/L in the obese group. HOMA-IR levels decreased with increasing FFA concentrations before the turning points (regression coefficient [β]= – 0.9, P=0.0111, for the nonobese group; β=0.2, P=0.5094, for the obese group) and then increased (β=0.9, P=0.0069, for the nonobese group; β=1.5, P=0.0263 for the obese group) after the points. Additionally, our study also identified that FFAs were associated with the prediabetes status in obese individuals.ConclusionFFA levels were associated with insulin resistance in nondiabetic subjects, and HOMA-IR in nonobese individuals was more sensitive to FFA changes. Monitoring and controlling plasma FFA levels in obese subjects is significant in decreasing insulin resistance and preventing diabetes.

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“…We have previously shown that acute hyperinsulinemia and hyperlipidemia, characteristic of metabolic syndrome, significantly decreases LH and FSH in normal weight women, providing a possible mechanism underlying the hypergonadotropic hypogonadism of obesity [ 6 ]. Others have shown that a very similar infusion of non-esterified fatty acids and insulin in lean research participants can result in insulin resistance and elevated TNF-alpha, although circulating cytokines were studied only after 48 hours [ 16 ]. Use of a multiplex cytokine array allowed profiling of a comprehensive panel of diverse markers of inflammation, given the limited serum samples available.…”

Section: Discussionmentioning

confidence: 99%

A randomised trial examining inflammatory signaling in acutely induced hyperinsulinemia and hyperlipidemia in normal weight women-the reprometabolic syndrome

et al. 2021

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Context Obesity, is a state of chronic inflammation, characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism. We have defined the accompanying decreased Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), ovarian steroids and reduced pituitary response to Gonadotropin-releasing Hormone (GnRH) as Reprometabolic syndrome, a phenotype that can be induced in healthy normal weight women (NWW) by acute infusion of free fatty acids and insulin. Objective To identify potential mediators of insulin and lipid-related reproductive endocrine dysfunction. Design, setting, participants Secondary analysis of crossover study of eumenorrheic reproductive aged women of normal Body Mass Index (BMI) (<25 kg/m2) at an academic medical center. Intervention Participants underwent 6-hour infusions of either saline/heparin or insulin plus fatty acids (Intralipid plus heparin), in the early follicular phase of sequential menstrual cycles, in random order. Euglycemia was maintained by glucose infusion. Frequent blood samples were obtained. Main outcome measures Pooled serum from each woman was analyzed for cytokines, interleukins, chemokines, adipokines, Fibroblast Growth Factor-21 (FGF-21) and markers of endoplasmic reticulum (ER) stress (CHOP and GRP78). Wilcoxon signed-rank tests were used to compare results across experimental conditions. Results Except for Macrophage Inflammatory Protein-1β (MIP-1β), no significant differences were observed in serum levels of any of the inflammatory signaling or ER stress markers tested. Conclusion Acute infusion of lipid and insulin, to mimic the metabolic syndrome of obesity, was not associated with an increase in inflammatory markers. These results imply that the endocrine disruption and adverse reproductive outcomes of obesity are not a consequence of the ambient inflammatory environment but may be mediated by direct lipotoxic effects on the hypothalamic-pituitary-ovarian (HPO) axis.

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A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects

Cited by 28 publications

References 35 publications

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people

A randomised trial examining inflammatory signaling in acutely induced hyperinsulinemia and hyperlipidemia in normal weight women-the reprometabolic syndrome

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