CS & LF - Evidence of Gut Microbial direct influence on metabolic parameters pertaining to Insulin Resistance

mice grown without gut bacteria gain a great deal of weight when that
bacteria is reintroduced even though they eat less; their leptin levels
go up; insulin sensitivity drops and they develop hyperglycemia; the
reintroduced microbiota triggered liver enzymes to produce more
triglycerides, upregulating acetyl-CoA carboxylase (ACC-1) and fatty
acid synthase (FAS) in the liver - both of which are targets of SREBP-1
(Sterol response element binding protein 1) and ChREBP; both ChREBP and
SREBP-1 are upregulated by the microbiota too; this promotes increased
monosaccharide uptake from the gut; the microbiota promote storage in
fat pads through the suppression of intestinal expression of a
circulating LPL (lipoprotein lipase) inhibitor; LPL (which can be
reduced by fasting) causes accumulation of fat; Fiaf (angiopoietin-like
protein 4) is produced by white/brown fat and the intestine and inhibits
LPL; Fiaf expression was very low in the microbiota mice; the problem
seems to do with how microbiota expand after the transition from
lipid/lactose-rich mother¹s milk to the low-fat/polysaccharide-rich chow
and how microbiota react with metabolic changes; this implies that
antibiotic use and insulin resistance are interrelated phenomena


in contrast to mice with a gut microbiota, germ-free (GF) animals are
protected against the obesity that develops after consuming a
Western-style, high-fat, sugar-rich diet; their persistently lean
phenotype is associated with increased skeletal muscle and liver levels
of phosphorylated AMP-activated protein kinase (AMPK) and its downstream
targets involved in fatty acid oxidation (acetylCoA carboxylase;
carnitine-palmitoyltransferase); GF knockout mice lacking
fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase
inhibitor whose expression is normally selectively suppressed in the gut
epithelium by the microbiota, are not protected from diet-induced
obesity; although GF Fiaf-/- animals exhibit similar levels of
phosphorylated AMPK as their wild-type littermates, they have reduced
expression of genes encoding Pgc-1alpha and enzymes involved in fatty
acid oxidation; GF animals are protected from diet-induced obesity by
(i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii)
increased AMPK activity [PMID 17210919]

LittleFighter wrote:This is a very interesting review:

http://www.nature.com/nrendo/journal/vaop/ncurrent/full/nrendo.2011.126.html

Targeting gut microbiota in obesity: effects of prebiotics and probiotics

Nathalie M. Delzenne, Audrey M. Neyrinck, Fredrik Bäckhed & Patrice D. Cani

Abstract

At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and their capacity to ferment nutrients and secrete bioactive compounds, these gastrointestinal microbes act as an environmental factor that affects the host's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. Experiments that compared germ-free and colonized mice or analyzed the influence of nutrients that qualitatively change the composition of the gut microbiota (namely prebiotics) showed that gut microbes induce a wide variety of host responses within the intestinal mucosa and thereby control the gut's barrier and endocrine functions. Gut microbes also influence the metabolism of cells in tissues outside of the intestines (in the liver and adipose tissue) and thereby modulate lipid and glucose homeostasis, as well as systemic inflammation, in the host. A number of studies describe characteristic differences between the composition and/or activity of the gut microbiota of lean individuals and those with obesity. Although these data are controversial, they suggest that specific phyla, classes or species of bacteria, or bacterial metabolic activities could be beneficial or detrimental to patients with obesity. The gut microbiota is, therefore, a potential nutritional and pharmacological target in the management of obesity and obesity-related disorders.