そもそもacetateの訳はきっと間違っている

The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity

導入

The obese state is characterized by increased adipose tissue mass and disturbed function resulting in systemic lipid spillover and low-grade inflammation, which may contribute to the development of comorbidities such as type 2 diabetes mellitus (T2DM) and cardiovascular disease.

：うんうん。

Additionally, gut microbes are able to ferment indigestible foods, such as dietary fibers, which, thereby, yields short-chain fatty acids (SCFA) as end products that may confer beneficial metabolic effects.

：腸内細菌に生かされてる。短鎖脂肪酸がいいらしい。

The most abundant SCFA are acetate, propionate, and butyrate with an approximate molar ratio of 60:20:20, respectively.

：酢酸塩、プロピオン酸、酪酸など。こいつらの受容体は、インスリン感受性の高い組織でmRNAによって発現が促進される？

Intracellularly, however, acetate may be converted to acetyl-CoA and incorporated in the tricarboxylic acid (TCA) cycle in various peripheral tissues.

：細胞内では、SCFAはアセチルCoAになってTCA回路に入り、エネルギー産生にかかわる。他にも、肝や骨格筋の酸化能/有酸素能(oxidative capacity?)を上げたり、脂肪酸合成＝エネルギー産生/消費？を促進したりする。

どうやって酢酸塩を摂取するか

①acidity regulator (pH control agent), preservative, or sequestrantとして

例）dried pastas, bread, liquid eggs, salt substitutes, coffee, coffee substitutes, processed meat, and smoked/frozen fish

②ethanol and vinegar

vinegar may provide rapid increments in plasma acetate levels due to its fast absorption in the upper digestive tract.

③腸内細菌の力を借りる

Microbial-derived acetate production is yielded by the fermentation of indigestible foods especially foods of acetogenic fibers (e.g., galacto-ligosaccharides, inulin). In addition, acetate may originate from microbial fermentation of residual peptides and fats.

酢酸塩とダイエット

・In a 12-week intervention in HFD-fed mice, Den Besten et al. found that oral sodium acetate supplementation incorporated into the diet (at 5%, weight/weight. proportion) resulted in a suppression of HFD-induced weight gain (~30%) compared to control mice fed an HFD.

・Similarly, Lu et al. showed that 16-weeks of oral sodium acetate supplementation (5%, wt./wt.) suppressed HFD-induced weight gain by 72% (p < 0.05) in comparison to control mice fed an HFD.

・In addition, a six-week intragastric administration of acetic acid (50, 250 mmol/L) to HFD-fed mice reduced weight gain (7% and 8%, respectively) and body fat accumulation in comparison to HFD alone .

：すてき！ただ、↓

In humans, long-term oral acetate supplementation or intravenous/gastric/colonic infusion studies with weight loss and energy expenditure as the primary outcome are limited.

：･･･。

Acetate accumulation in the hypothalamus was shown to affect appetite regulation through the glutamate-glutamine transcellular cycle, which resulted in increments in lactate and gamma aminobutyric acid (GABA) production, after both intraperitoneal acetate injections and after colonic fermentation of ¹³C-labelled carbohydrate.

：酢酸塩はBBBを通過して脳脊髄液にも入れる。視床下部で食欲をあやつる。

Hypothalamic acetate administration showed inactivation of AMPK and activation of ACC (via decreased phosphorylation), which suggests that acute administration of acetate may increase hypothalamic ACC activity. ACC activation may increase malonyl-CoA, which may lead to a reduction in food intake through the expression of orexigenic and anorexigenic neuropeptides in the hypothalamus via two mechanisms: (i) via the interaction of malonyl-CoA with signaling proteins or (ii) via inhibition of carnitine/palmitoyl-CoA transferase (CPT) that prevents the entry of the long-chain fatty acids to the mitochondrion.

：視床下部でむつかしいいろーんな作用を介して、とりあえず、食欲をおとす！しかも、腸管で出る食欲ホルモンも減るそうな。

Recently, acute colonic infusions showed increments in fasting fat oxidation and energy expenditure in humans.

：酢酸塩たべると脂肪酸の酸化が促進されてエネルギー消費。

・A 12-week vinegar intervention significantly lowered body weight with low (0.75 g) and high (1.5 g) acetate doses versus placebo (0 g) in a dose-dependent manner.

・In addition, a crossover study in overweight-obese subjects, the consumption of Kimchi (fermented Korean dish, unclear % of acetic acid) vs. unfermented dish reduced body fat (~1%), body weight (~1.5 kg), and BMI (0.6 kg/m²) after two weeks.

・In a similar crossover study, in overweight women, fermented Kimchi (unclear % of acetic acid) decreased Firmicutes/Bacteroidetes ratio, which has been associated with weight loss.

Oral vinegar (4%–8% acetic acid) administrations may rapidly increase circulating acetate and its co-ingestion with carbohydrates (50–75 g), which seems more effective for glucose lowering and insulinemic responses.

：酢→血中酢酸塩上昇＋一緒に炭水化物とりこみ上昇。なんで一緒に炭水化物とりこむのに"effective for glucose lowering"なの？インスリン出るから？"insulinemic responses"だからそうなのか？

・Supplementation of acetic acid (unspecified vinegar) in healthy subjects together with a test meal resulted in reduced postprandial glucose concentration (~35%, during 30–70 min), putatively, through a delayed gastric emptying.

・Similarly, white vinegar (6% acetic acid) administrations (18, 23, and 28 mmol/L) in combination with white wheat bread (50 g) in healthy subjects lowered glycemic (highest dose at 30–45 min) and insulinemic (highest dose at 15–30 min) postprandial responses.

：insulinemic responsesをlowerするなら、やっぱりGI的なので一緒に炭水化物とりこむのに何でこうなるのか、分からない。

・In addition, acetic acid lowered the glycemic index (GI) and increased the satiety score postprandially at 30, 90, and 120 min using a subjective rating scale.

：満腹感えられるのはよいこと。

・Another study in healthy subjects reported that a vinaigrette (28 g white vinegar, 6% acetic acid) on a potato meal reduced GI and insulinemic index (43 and 31%, respectively).

：すごーい。

For instance, a study in individuals with IGT showed that wine vinegar (6% acetic acid) administration decreased arterial plasma insulin (by 33%) and increased muscle glucose uptake (by 35%) after a meal test, as compared to the placebo (50 mL water).

：耐糖能異常ある人でも、よさそう。

Additionally, in T2DM individuals, oral wine vinegar administration (1.2 g acetic acid) decreased incrementalAUC 120 min of glucose (41%) only after a high GI meal test (mashed potatoes and low-fat milk) but not after a low GI meal test.

Acetate administration has been shown to affect whole-body as well as intracellular lipolysis in adipocytes in in vitro and in vivo animal and human studies.

Ge et al. reported that acetate-mediated activation of GPR43 in 3T3-L1 adipocytes was accompanied by an inhibition of the lipolytic response within a physiological range of 100–300 µmol/L.

：酢酸塩によって脂肪分解が抑制される？(脂肪分解＝トリグリセリドが脂肪酸とグリセロールに加水分解されること。交感神経賦活やグルカゴン、ステロイドホルモンなどでも起こる。)

Crouse et al. showed that orally administered sodium acetate (given in two doses 143 mg/kg initially and 71 mg/kg 30 min later) increased plasma acetate by three-fold to four-fold and decreased FFA plasma concentrations by 25% in healthy humans within 20 min after ingestion.

：ヒトでもおんなじ。

Thus, both animal and human data show an antilipolytic effect of acetate that may decrease lipid overflow to peripheral insulin-sensitive tissues (e.g., skeletal muscle), which may possibly improve insulin sensitivity and decrease hypothalamic inflammation.

：脂肪酸がないことがいいことなのかな。そもそも生化学のエネルギー産生とか全然わかってないわ。復習しよ。

Acetate may affect the proliferation and differentiation of adipocytes, which contributes to adipose tissue morphology, browning, and function. This can induce high thermogenic activity with the potential to enhance oxidative capacity.

In summary, although the human evidence is limited, acetate seems to play a role in adipogenesis and browning of WAT. Together with the antilipolytic effects, acetate may restructure adipose tissue morphology and improve adipose tissue functioning as well as energy metabolism and overall metabolic health.

 ：脂肪細胞の増殖･分化にも影響する＝褐色脂肪細胞をつくる？

Intracellularly, acetate may be rapidly assimilated and metabolized through the TCA cycle in the mitochondrial matrix, contribute to the Acetyl-coA pool, and/or modulate signaling mechanisms involved in muscle lipid oxidation.

：ちょっとよく分からん。

酢酸塩と糖尿病

With respect to glucose metabolism, acetate supplementation (0.2 g acetic acid/100 g diet for 2 h) increased glycogen storage (1.1 fold) and decreased glycolysis in the gastrocnemius as compared to the control (no acetate) in Sprague-Dawley rats. In support, as mentioned above, increments in the protein expression of GLUT4 may suggest a modulatory role in glucose homeostasis. In summary, acetate may modulate skeletal muscle lipid and glucose metabolism possibly through activation (phosphorylation) of AMPK. 

：酢酸塩たべるとグリコーゲンの貯蔵がふえて、糖新生がへる。GLUT4発現がふえて血糖コントロールよくなる。のか。

こんなかんじで、acetogenic fiberたべると血糖は下がるわ、インスリン感受性は上がるわ、脂質は下がるわ、などなど。ラクツロースとかイヌリン？ただ、fiber摂取しても血中acetateかわらんっていうstudyもある。種類がだいじ？

First, a probiotic intervention in mice, (Bifidobacterium animalis ssp. lactis GCL2505) modified microbial community (increased Bifidobacterium and Lactobacillus), increased acetate (caecal and plasma) levels and improved glucose tolerance, which was accompanied by a reduction of adipocyte cell size.

： この2つの菌はほかのstudyでも言われてて、O157を寄せ付けなかったとか･･･。

Another important bacterium, A. muciniphila, has been associated with improvements in adiposity in both rodents and humans and loss of A. muciniphila has been reported to impair gut integrity and increase insulin resistance in rodents.

：こいつはacetateの産生にもかかわる大事なやつらしい。

まとめ

Acetate has an important regulatory role in body weight control, and insulin sensitivity through effects on lipid metabolism and glucose homeostasis (as summarized in Figure 1).

With respect to oral acetate administrations (vinegar), improvements on glucose homeostasis have been reported, and attributed to acetic acid. Future vinegar supplementations should specify its composition (e.g., acetic acid percentage, polyphenols). Moreover, future prebiotic/probiotic/vinegar studies should consider that responses may differ between healthy individuals and pre-diabetic individuals, as shown in vinegar administrations.

難しくって、何回も意識を飛ばしながら読んだ。わかったことは

・酢酸塩はからだに良い(体重減る、血糖へる)

・酢をのむか、短鎖脂肪酸をたべるかして摂取する　ベストは不明

・あとはいい菌を飼うか

・満腹感でるし、脂肪酸酸化も促進するし、低GI効果もある

・そのほかエネルギー産生についても書いてあったけど難しかった

ほんまわたしアホやな。と思った。